Bodily fluid sample collection and transport

ABSTRACT

Bodily fluid sample collection systems, devices, and method are provided. The sample is collected at a first location and subjected to a first sample processing step. The sample may be shipped to a second location and subjected to a second sample processing step that does not introduce contaminants into a plasma portion of the sample formed from the first processing step. The sample may also be mixed with other material(s) in the collection device.

BACKGROUND

A blood sample for use in laboratory testing is often obtained by way ofvenipuncture, which typically involves inserting a hypodermic needleinto a vein on the subject. Blood extracted by the hypodermic needle maybe drawn directly into a syringe or into one or more sealed vials forsubsequent processing. When a venipuncture may be difficult orimpractical such as on a newborn infant, a non-venous puncture such as aheel stick or other alternate site puncture may be used to extract ablood sample for testing. After the blood sample is collected, theextracted sample is typically packaged and transferred to a processingcenter for analysis.

Unfortunately, conventional sample collection and testing techniques ofbodily fluid samples have drawbacks. For instance, except for the mostbasic tests, blood tests that are currently available typically requirea substantially high volume of blood to be extracted from the subject.Because of the high volume of blood, extraction of blood from alternatesample sites on a subject, which may be less painful and/or lessinvasive, are often disfavored as they do not yield the blood volumesneeded for conventional testing methodologies. In some cases, patientapprehension associated with venipuncture may reduce patient compliancewith testing protocol. Furthermore, the transportation of small volumesof sample fluid, while still maintaining sample integrity, can beproblematic.

SUMMARY

At least some of disadvantages associated with the prior art areovercome by at least some or all of the embodiments described in thisdisclosure. Although the embodiments herein are typically described inthe context of obtaining a fluid sample such as but not limited to ablood sample, it should be understood that the embodiments herein arenot limited to blood samples and can also be adapted to acquire otherfluid(s) or bodily sample(s) for analysis.

In one embodiment described herein, a device is provided for collectinga bodily fluid sample. In embodiments, the bodily fluid may be blood. Inembodiments where blood is collected, this embodiment may be useful foraccurately collecting small volumes of bodily fluid sample that areoften associated with non-venous blood draws. In one non-limitingexample, the sample volume is about 1 mL or less. Optionally, the samplevolume is about 900 μL or less. Optionally, the sample volume is about800 μL or less. Optionally, the sample volume is about 700 μL or less.Optionally, the sample volume is about 600 μL or less. Optionally, thesample volume is about 500 μL or less. Optionally, the sample volume isabout 400 μL or less. Optionally, the sample volume is about 300 μL orless. Optionally, the sample volume is about 200 μL or less. Optionally,the sample volume is about 100 μL or less. Optionally, the sample volumeis about 90 μL or less. Optionally, the sample volume is about 80 μL orless. Optionally, the sample volume is about 70 μL or less. Optionally,the sample volume is about 60 μL or less. Optionally, the sample volumeis about 50 μL or less.

In one non-limiting example, this device can be used to split the bodilyfluid sample directly into two or more different portions that are thendeposited into their respective sample vessels. In one non-limitingexample, the device comprises a first portion having at least two samplecollection channels configured to draw the fluid sample into the samplecollection channels via a first type of motive force, wherein one of thesample collection channels has an interior coating designed to mix withthe fluid sample and another of the sample collection channels hasanother interior coating chemically different from said interiorcoating. The sample collection device includes a second portioncomprising a plurality of sample vessels for receiving the bodily fluidsample collected in the sample collection channels, the sample vesselsoperably engagable to be in fluid communication with the collectionchannels, whereupon when fluid communication is established, the vesselsprovide a second motive force different from the first motive force tomove a majority of the bodily fluid sample from the channels into thesample vessels. The sample vessels may be arranged such that mixing ofthe fluid sample between the vessels does not occur. This device may beused to collect blood or other bodily fluid. Blood collection from veinsmay be relatively rapid; however, non-venous blood draws may take alonger period of time to obtain a desired volume of sample and the earlyintroduction of a material such as an anti-coagulant which may coat thechannels, can prevent premature clogging of the channels duringcollection.

In another embodiment described herein, a device is provided forcollecting a bodily fluid sample. The device comprises a first portioncomprising a plurality of sample collection channels, wherein at leasttwo of the channels are configured to simultaneously draw the fluidsample into each of the at least two sample collection channels via afirst type of motive force. The device may also include a second portioncomprising a plurality of sample vessels for receiving the bodily fluidsample collected in the sample collection channels, wherein the samplevessels have a first condition where the sample vessels are not in fluidcommunication with the sample collection channels, and a secondcondition where the sample vessels are operably engagable to be in fluidcommunication with the collection channels, whereupon when fluidcommunication is established, the sample vessels provide a second motiveforce different from the first motive force to move bodily fluid samplefrom the channels into the sample vessels. In embodiments, motive forceto move a bodily fluid may include motive force derived from capillaryaction, from reduced pressure (e.g., vacuum or partial vacuum drawingfluid into a location having reduced pressure), from increased pressure(e.g., to force a fluid away from a location having increased pressure),from wicking material, or from other means.

In a still further embodiment described herein, a method is providedcomprising metering a minimum amount of sample into at least twochannels by using a sample collection device with at least two of thesample collection channels configured to simultaneously draw the fluidsample into each of the at least two sample collection channels via afirst type of motive force. After a desired amount of sample fluid hasbeen confirmed to be in the collection channels, fluid communication isestablished between the sample collection channels and the samplevessels, whereupon the vessels provide a second motive force differentfrom the first motive force use to collect the samples to move bodilyfluid sample from the channels into the vessels. In some alternativeembodiments, devices that use only a single channel to collect the bodyfluid or devices that have a plurality of channels but do not collectthem simultaneously are not excluded. Optionally, the collection ofsample fluid is performed without the use of a wicking material.

In one embodiment, there is a discrete amount of time between samplecollection and introduction of the sample into a sample pre-processingdevice. In one non-limiting example, the process is a non-continuousprocess. The sample collection occurs in one processing station and thenthe sample is taken to a second station. This second station may be inthe sample building. Optionally, the second station may be located atanother location where the sample needs to be walked, driven, flown,conveyor-ed, placed in a transport device, or placed in a transportcontainer to reach the second location. In this manner, there is adiscrete break in the processing to allow for time associated withsample transport.

In another embodiment herein, separator gel(s) can also be included inthe sample vessels such that the gels will separate cell-free fractionsof whole blood from the cellular or other solid or semi-solid portionsof the sample. Such a gel or other similar separator material may beincluded in the sample vessel prior to, during, or after sample has beenintroduced into the sample vessel. The separator material may have adensity between that of the cells and solution components, so that thematerial separates the sample components by flowing to a positionbetween the solution and non-solution sample layers during separationsuch as by centrifugation. Following centrifugation, the separatormaterial stops flowing and remain as a soft barrier between the layers.In some embodiments, the separator material can be further processed toharden into a more rigid barrier. In on non-limiting example, theseparator material may be a UV-curable material such as but not limitedto thixotropic gel of sorbitol-based gelator in a diacrylate oligomer.The sample vessel may have the entire vessel or optionally, on thatportion with the UV-curable material exposed to UV light for a period oftime such as but not limited to 10 to 30 seconds to harden the material.Such hardening may involve cross-linking of material in the UV-curablematerial. Optionally, the UV curable material may be used in conjunctionwith traditional separator gel material such that only one side (thesolution side or the solid side) is in contact with the UV curedmaterial. Optionally, the UV cured material may be used with a thirdmaterial such that the UV cured material is between two separatormaterials and is not in direct contact with the solution andnon-solution portions of the sample.

Samples of bodily fluid may be collected by the devices disclosed anddescribed herein. Methods of collecting bodily fluid using these devicesare disclosed and described herein. Samples of bodily fluid, e.g.,samples that have been collected by the devices and/or methods disclosedand described herein, may be transported from a sample collection siteto one or more other sites.

In at least one embodiment described herein, methods are provided forthe physical transport of small volumes of bodily fluid in liquid formfrom one location to another location. By way of nonlimiting example,the samples are collected in liquid form at a collection site,transported in liquid form, and arrive at an analysis site in liquidform. In many embodiments, the liquid form during transport is not heldin a porous matrix, wicking material, webbing, or similar material thatwould prevent sample from being extracted in liquid form at thedestination site. In one embodiment, small volume of sample in eachsample vessel is in the range of about 1 ml to about 500 microliters.Optionally, small volumes are in the range of about 500 microliters toabout 250 microliters. Optionally, small volumes are in the range ofabout 250 microliters to about 100 microliters. Optionally, smallvolumes are in the range of about 100 microliters to about 50microliters. Optionally, small volumes are in the range of about 80microliters to about 40 microliters. Optionally, small volumes are inthe range of about 40 microliters to about 1 microliter. Optionally,small volumes are in the range of about 1 microliter to about 0.3microliters. Optionally, small volumes are in the range of about 0.3microliters or less.

As disclosed and described herein, a transport container may include acomponent configured to receive and retain a sample vessel. Inembodiments, a component configured to receive and retain a samplevessel may be configured to receive and retain a plurality of samplevessels. In embodiments, such a component may comprise a flat sheet,such as, e.g., a tray. In embodiments, such a component (e.g., a flatsheet) may comprise an opening (e.g., a slot, aperture or receptacle)having an internal surface configured to accept a sample vessel. Inembodiments, a transport container may include a component comprising aplurality of openings (e.g., slots, apertures or receptacles) eachhaving an internal surface configured to accept a sample vessel. Inembodiments, such an internal surface may be, at least in part,substantially complementary to the outer surface, or a portion thereof,of a sample vessel.

In another embodiment described herein, the transport container mayprovide a high density of sample vessels per unit area held in a fixedmanner during transport, but removable at the destination location. Inone non-limiting example, the sample vessels are positioned in an arraywhere there are at least six sample vessels per square inch, whenviewing the array from top down. Optionally, there are at least eightsample vessels per square inch, when viewing the array from top down.Optionally, there are at least ten sample vessels per square inch, whenviewing the array from top down. Any traditional techniques that shipmultiple samples typically use large bags where the sample vesselstherein are in a loose, unconstrained manner. In some embodiments, thetransport container can hold certain sample vessels such as those fromthe same subject, closer together relative to horizontal or otherspacing to adjacent sample vessels so that they can be visuallyidentified as being from a common subject. Optionally, the transportcontainer has openings to receive carriers that hold one or more samplevessels together, wherein those vessels have a common denominator suchas but not limited to being from the same subject.

In embodiments, the sample vessels are adapted to aid in maintaining thesamples in liquid form. In embodiments, the sample is treated prior toits arrival in a sample vessel in a manner adapted to maintain thesample in liquid form. For example, a sample vessel may include ananti-coagulating agent, or a sample may be treated with ananti-coagulating agent prior to, or during, transport to or into asample vessel. In embodiments, an anti-coagulating agent may be selectedfrom the group consisting of heparin (e.g. lithium heparin or sodiumheparin), ethylenediaminetetraacetic acid, 4-hydroxycoumarins, vitamin Kantagonist (VKA) anticoagulant, an anti-coagulant, or other additive. Inaddition to the high density per unit area, some embodiments of thetransport container also contain a high diversity of samples, includingthose that contain samples from a plurality of different subjects. Byway of non-limiting example, the transport container may have foursamples from one subject, two samples from another subject, and so-onuntil the majority or all of the available openings in the transportcontainer are filled.

It should be understood that each of the samples can be destined forindividually selected analysis and at least in one embodiment, are notgrouped in the transport container based on tests to be performed. Byway of non-limiting example, not all of the samples in the transportcontainer are collected for the same test. A traditional test system mayonly group together for transport those samples destined for the exactsame test. In at least one of the embodiments herein, there is adiversity of samples, each designated to receive its own set of tests.In such an embodiment, grouping in the transport container is notrestricted to only those samples targeted for the same test. This canfurther simplify sample processing because sample transport does notneed to be further segregated based on tests to be performed. Someembodiments of the transport container contain samples from at leastthree or more different patients. Some embodiments of the transportcontainer contain samples from at least five or more different patients.Some embodiments of the transport container contain samples from atleast ten or more different patients. Some embodiments of the transportcontainer contain samples from at least twenty or more differentpatients.

By way of non-limiting example, one embodiment described herein mayoptionally use tray(s) that have slots for holding the sample vesselsand/or sample vessel holders. In one embodiment, the tray may alsodouble as a holding device during storage in a cooling chamber whileawaiting more samples or transport. In one embodiment, the tray canitself also be cleaned and sterilized, because in some embodiments, thetray is removable from the transport container. In some embodiments, thetray in the transport container may be held in manner parallel to acover of the transport container. Optionally, the tray may be heldinside the transport container at an angle to the cover of the transportcontainer. Optionally, the tray is irremovably fixed to the transportcontainer. Optionally, the tray is integrally formed with the transportcontainer itself. Optionally, multiple trays of same or different sizeor configuration may be placed inside the transport container.

In yet another embodiment described herein, methods are provided forshipping small volume sample vessels using a transport container withintegrated thermal control unit and/or material that provides activeand/or passive cooling. In one embodiment, the thermal control materialmay be but is not limited to embedded phase change material (PCM)material that maintains the temperature at a prior, or desiredtemperature. By way of non-limiting example, the phase change materialcan oppose changes in temperature around the critical temperature wherethe material would undergo a phase change. If the PCM is embedded, thevessel and the passive cooling element may be one and the same.Optionally, the transport container may use an active cooling system.Optionally, the transport container may use an active cooling system tokeep and/or extend cooling time associated with a passive coolingcomponent. In embodiments, a transport container may include materialhaving a high heat capacity (i.e., high as compared to material such asa plastic or polymeric material), and may include a mass of such a highheat capacity material effective to maintain at least a portion of thetransport container at or near to a desired temperature for an extendedperiod of time.

Optionally, the method comprises a single step for transferring multiplesample vessels from different subjects from a controlled temperaturestorage area into a transport container. By way of non-limiting example,this single step can transfer twenty-four or more sample vessels at onetime from a storage location into a fixed position in the transportcontainer. Optionally, this single step can transfer thirty-six or moresample vessels at one time from a storage location into a fixed positionin the transport container. Optionally, this single step can transferforty-eight or more sample vessels at one time from a storage locationinto a fixed position in the transport container. In such embodiments,the tray may be initially in a controlled thermal environment such asbut not limited to a refrigerator wherein samples from various subjectsare collected over time until a desired number is reached. In one suchembodiment, the tray holding the sample vessel(s) in the transportcontainer is the same tray holding the sample vessels in the storagearea. Optionally, the tray may be the same as the storage holder that isused to hold samples prior to loading into the transport container.Because the same tray which holds the sample vessels will be used in thetransport container, there is reduced risk that samples will be lostduring this transfer, left out in a non-regulated thermal environment,or the like. Because substantially all sample vessels in the tray areaccumulated in the controlled thermal storage area and then transferredin a single step, the samples all experience substantially the samethermal exposure while being transferred from the control thermalstorage area into the transport container. Because sample vesselsexperience substantially the same exposure, there is less variabilitysample-to-sample due to different exposure times.

Optionally, the method comprises using an individually addressablesample vessel configuration. Optionally, groups of sample vessels suchas those in a common carrier may be addressed in the pre-defined groups.Optionally, even sample vessels in a common carrier may be individuallyaddressed. Although not a requirement for all embodiments herein, thiscan be of particular use when loading and/or unloading samples, samplevessels, and/or sample holders from the tray.

Some embodiments may use yet another container (an “outerbox”) outsidethe transport container to provide further physical protection and/orthermal control capability. One or more of the transport container canbe placed inside the outerbox and the combination may be shipped fromone location to a destination location. By way of non-limiting example,this can be in the form of a corrugated plastic outerbox, where theouterbox is configured to at least partially encase or enclose atransport container. In embodiments, an outerbox provides thermalinsulation for a transport container enclosed therein. Some embodimentsmay use closed-cell extruded polystyrene foam outerbox. Some embodimentsof the outerbox may be formed from thermoformed panels. In someembodiments, an outerbox may have grips, handles, pads, wheels, latches,stays, and/or other features useful in holding, manipulating, securing,protecting, transporting, or otherwise controlling the position,orientation, and/or access to the contents of the outerbox. Someembodiments of the outerbox may have its own active and/or passivethermal control unit. In embodiments, an outerbox provides cooling andthermal insulation for one or more transport containers enclosedtherein. One or more embodiments of the outerbox may be configured tohouse one or more transport containers. Optionally, this container canalso provide additional thermal control to the transport container byproviding a thermally regulated environment between a desiredtemperature range to the transport container(s) therein. Optionally,this temperature range is between about 1 to 10° C., optionally 2 to 8°C., or between 2 to 6° C.

In yet another embodiment described herein, a method is provided forthermally characterizing the transport container after a number ofcooling cycles. By way of non-limiting example, after certain number ofcycles, the transport container may be thermally characterized to ensurethat the container is continuing to perform within a desired range.

Some embodiments of the container and/or tray may include a thermalchange indicator. In one non-limiting example, the indicator isintegrated on a visible surface of the transport container, tray, and/oron the outerbox. In one non-limiting example, thermochromic ink may beused as an indicator of thermal change, particularly if the thermalchange resulted in temperatures outside a desired range. In oneembodiment, this indicator may be configured to have the entire boxand/or tray change color. The change can be reversible or irreversible.Optionally, the indicator is positioned to be on only select portions ofthe transport container and/or tray, not the entire container or tray.

In one embodiment described herein, a method is provided comprisingcollecting a bodily fluid sample on a surface of a subject, whereincollected sample is stored in one or more sample vessels; providing atransport container to house at least two or more sample vessels in afirst orientation; and arranging to have the sample vessels shipped inthe transport container from a first location to a second location,wherein each of the sample vessels arrives at the second locationholding a majority of its bodily fluid sample in a non-wicked,non-matrixed form that is removable from the sample vessels in liquidform and wherein the amount of sample in each of the sample vessels doesnot exceed about 2 ml. In embodiments, the amount of sample in each ofthe sample vessels does not exceed about 1 ml, or does not exceed about500 μL, or does not exceed about 250 μL, or does not exceed about 100μL, or does not exceed about 50 μL, or less.

In another embodiment described herein, a method is provided forshipping a plurality of sample vessels, the method comprising: providinga container configured to house at least five or more sample vesselseach containing capillary blood; and arranging to have the samplevessels shipped in the transport container from a first location to asecond location, wherein each of the sample vessels arrives holding amajority of its capillary blood in a liquid, non-wicked form that isremovable from the sample vessels for further processing, and whereinthe amount of capillary blood in each of the sample vessels does notexceed about 2 ml. In embodiments, the amount of capillary blood in eachof the sample vessels does not exceed about 1 ml, or does not exceedabout 500 or does not exceed about 250 or does not exceed about 100 ordoes not exceed about 50 or less.

In another embodiment described herein, a method is provided forshipping a plurality of sample vessels for containing biological sample,the method comprising: providing a container configured to house atleast five or more of the sample vessels, wherein the amount of samplein each of the sample vessels does not exceed about 2 ml; and shippingthe container and sample vessels from a first location to a secondlocation, wherein each of the sample vessels arrives at the secondlocation holding a majority of its biological in a liquid, non-wickedform that is removable from the sample vessels for further processing.In embodiments, the amount of sample in each of the sample vessels doesnot exceed about 1 ml, or does not exceed about 500 or does not exceedabout 250 or does not exceed about 100 or does not exceed about 50 μL,or less.

In another embodiment described herein, a method is provided forshipping a plurality of sample vessels containing capillary blood, themethod comprising: providing a container having a thermally-regulatedinterior region that is configured to house at least five or more samplevessels in a controlled configuration such that at least one coolingsurface of the container is directed towards the sample vessels andtransmits a controlled release of thermal cooling in accordance with atemperature profile that maintains the interior region between about 1to 10° C. during transport and without freezing the blood samples; andshipping the container from a first location to a second location,wherein each of the sample vessels arrives holding a majority of itscapillary blood in a liquid, non-wicked form that is removable from thesample vessels for further processing.

In another embodiment described herein, a method is provided forshipping a plurality of blood sample vessels, the method comprisingshipping a container having a thermally-controlled interior that isconfigured to house 10 or more sample vessels in an array configuration,wherein each of the vessels holds a majority of its blood sample in afree-flowing, non-wicked form and wherein there is about 1 ml or less ofblood in each of the vessels and each of the vessels has an interiorwith at least a partial vacuum atmosphere; wherein sample vessels areheld in the array configuration to position said sample vessels atcontrolled distance and orientation from a cooling surface, whereinthere is at least one preferential thermal pathway from the surface tothe sample vessel.

In another embodiment described herein, a method is provided forshipping a plurality of sub-1 ml sample vessels, the method comprisingmixing sample with anti-coagulant prior to transferring sample into eachof the sample vessels; associating each of the sample vessels with asubject and a panel of requested sample tests; and shipping athermally-controlled container that houses the plurality of sub-1 mlsample vessels in an array configuration, wherein each of the vesselsholds a majority of its sample in a free-flowing, non-wicked form,wherein vessels are arranged such that there are at least two vessels ineach container is associated with each subject, wherein at least a firstsample includes a first anticoagulant and a second sample includes asecond anticoagulant in the matrix.

In another embodiment described herein, a method is provided comprisinga) placing said plurality of sample vessels in a temperature controlledtransport container comprising a controlled uniform thermal profile,high heat of fusion material configured to be in thermal communicationwith the sample vessels, wherein the material does not cause freezing ofsample fluid in the sample vessels; b) placing said thermal profiletransport container in a product cavity defined by at least top andbottom walls of a transport container; c) placing an active coolingdevice in thermal communication with said cavity whereby said coolingdevice is adapted to cool said cavity upon activation, said sorptioncooling device comprising an absorber positioned so as to dissipate heatgenerated in said absorber outside of said product cavity; d) activatingsaid cooling device to initiate cooling of said cavity; e) transportingsaid transport container from a first location to a second location; andf) removing said product from said cavity.

In another embodiment described herein, a method of shipping a pluralityof sub-1 ml sample vessels is provided comprising: shipping athermally-controlled container that houses the plurality of sub-1 mlsample vessels in an array configuration, wherein each of the vesselsholds a majority of its sample in a free-flowing, non-wicked form andwherein vessels are arranged such that there are at least two vessels ineach container is associated with each subject, wherein at least a firstsample includes a first anticoagulant and a second sample includes asecond anticoagulant in the matrix.

It should be understood that any of the embodiments herein can beadapted to have one or more of the following features. In onenon-limiting example, the bodily fluid sample is blood. Optionally, thebodily fluid sample is capillary blood. Optionally, collecting thebodily fluid sample comprises making at least one puncture on thesubject to release the bodily fluid, wherein the puncture is not avenipuncture. Optionally, collecting comprises using at least onemicroneedle to make at least one puncture on the subject. Optionally,collecting comprises using at least one lancet to make at least onepuncture on the subject.

Optionally, the puncture may be formed by finger prick. Optionally, thepuncture is formed by pricking skin on a forearm of the subject.Optionally, the puncture is formed by pricking skin on a limb of thesubject. Optionally, the puncture is formed by pricking at least one earof the subject. Optionally, the surface is the skin of the subject.Optionally, other non-finger alternate sites can be targeted to obtainat least one biological sample from the subject. Optionally, a solidnon-coring penetrating member may be used to release the biologicalsample from the subject. Optionally, other embodiments may have a coringdevice that may be but is not limited to a coring needle or other coringpenetrating member to both cause a release of liquid biological sampleand to obtain a non-liquid sample in the coring penetrating member, suchas but not limited to a tissue sample. Some embodiments may use at leastone coring penetrating member and at least one non-coring penetratingmember. Some embodiments may use a blade for creating the wound. Somemay use a puncture-type motion while others may use a cutting typemotion. Any of these penetrating member(s) may be configured for use forone or more of the target sites thereon.

Optionally, the transport container has an interior that is initially atsub-atmospheric pressure. Optionally, the sub-atmospheric pressure is atleast a partial vacuum. Optionally, the interior of the transportcontainer is at a sub-atmospheric pressure that is at least at apressure below ambient pressure. Optionally, the sub-atmosphericpressure is selected to provide sufficient force to draw a desiredvolume of sample into the sample vessel. Optionally, the transportcontainer contains at least five or more sample vessels. Optionally, thetransport container ships bodily fluid samples from a plurality ofdifferent subjects. Optionally, information associated with each of thesample vessels determine what tests will be run on the bodily fluidsample therein. Optionally, the transport container is placed insideanother container during shipping. Optionally, the method furthercomprises pre-processing sample in the sample vessels prior to shippingto the second location. Optionally, at least a portion of the sample maybe collected and dried, such as but not limited to collection on a papersample collector. There may be multiple “spots” on the collector for thesample to be collected and then shipped on such paper sample collectionmember. The dried sample may be shipped together with the containerhaving the liquid sample. Both may be coded with the same identifier orat least one that associates both collectors with the same subject.

Optionally, the transport container has a sample vessel array density ofat least about 4 vessels per square inch. Optionally, a cooling surfacein the transport container provides a temperature profile within adesired range for sample vessels in the vessel. Optionally, the samplevessels are individually addressable. Optionally, the method furthercomprises using a cooled tray to hold the samples vessels in a coolingchamber prior to loading the vessels into the container and the sametray is used to hold the sample vessels in the vessel, wherein thesamples are placed into container with the cooled tray. Optionally,sample vessels are arranged such that there are at least two vessels ineach container with bodily sample fluid from the same subject, whereinat least a first sample includes a first anticoagulant and a secondsample includes a second anticoagulant in the matrix. Optionally, thefluid sample comprises capillary blood for use in testing by FDA-clearedor FDA-certified assay devices and procedures, or testing by aCLIA-certified laboratory. Optionally, the fluid sample comprises bloodfor use in testing by FDA-cleared or FDA-certified assay devices andprocedures, or testing by a CLIA-certified laboratory. Optionally, ahousing providing a controlled thermal profile and high heat of fusionmaterial providing at least one cooling surface facing the vessels.Optionally, a high heat of fusion material is embedded in material usedto form the vessel. Optionally, a controlled thermal profile, high heatof fusion material comprises about 30% to 50%. Optionally, a controlledthermal profile, high heat of fusion material comprises about 10% to30%. Optionally, the method further comprises a housing of metallicmaterial having a resting temperature less than ambient temperature.

Optionally, the method further comprises scanning an information storageunit on each sample at the receiving site and automatically placing thevessel into a cartridge. Optionally, the method further comprisesscanning an information storage unit on each sample at the receivingsite and automatically placing the vessel into a cartridge. Optionally,the method further comprises using the same tray to hold sample vesselsin the array configuration when in a refrigeration device prior totransport and in the transport container during transport. Optionally,the method further comprises using a tray for holding the sample vesselsthat comprises a highly thermally conductive material. Optionally, thetray comprises a plurality of slots having a shape to hold samplevessels holders in a preferential orientation. Optionally, the tray isconfigured to directly engage sample vessel holders. Optionally, a traylocking mechanism is used to hold the tray within the vessel, whereinthe tray locking mechanism releases the tray only upon application ofmagnetic force. Optionally, the method comprises maintaining atemperature range in the 2° C. to 8° C. during transport. Optionally,the method further comprises a temperature control material thatmaintains above freezing but about 10° C. or less during transport.Optionally, the method comprises using a temperature threshold detectorto indicate if the sample vessel reaches a temperature outside athreshold level. Optionally, the method further comprises scanning avessel in the tray prior to shipping to determine if a processing stepon the sample had not been performed; using a processor to perform orre-perform a step. Optionally, the method further comprises asingle-step loading of the sample vessel(s) into the tray and then asingle-step loading of the tray into the transport container.

Optionally, the transport container has a first surface configured todefine a thermally conductive pathway to the controlled thermal profile,high heat of fusion material in the transport container. Optionally, thefirst surface is configured to be in direct contact with another surfacecooled by a sorption cooling device. Optionally, the method comprisessimultaneous bar code scanning of sample vessels in the tray.Optionally, the method comprises simultaneous bar code scanningundersides of sample vessels in the tray. Optionally, the methodcomprises bar code scanning rows of sample vessels. Optionally, themethod comprises bar code scanning undersides of rows of sample vessels.Optionally, the method comprises shipping a plurality of the samplevessels in an inverted orientation. Optionally, the method comprisesshipping a plurality of the sample vessels wherein blood cells andplasma are separated by a barrier material in the sample vessels.Optionally, the method comprises opening the transport container byunlocking it and opening it, wherein at least one hinge holds two piecestogether. Optionally, the tray has at least one magnetic contact pointfor removing the tray from the vessel. Optionally, a computer controlledend effector is used to load and/or unload sample vessels from thetransport container, wherein before, during, or after unloading, areader obtains information from at least one information storage unitattached to one or more sample vessels. It should be understood thatalthough the transport container is often used for transport, it canalso be used as a storage container for the tray and/or sample vesselswhen the transport container is not used for transport. Accordingly, theuses for the container are not limited to transport and other suitableuses for any of the embodiments are not excluded.

In yet another embodiment herein, a thermal-controlled transportcontainer is provided for use in shipping a plurality of sample vessels,the transport container comprising: a container having at least a top,bottom, and side walls together defining a cavity, wherein at least oneof said top, bottom and side walls comprises a phase change material; aframe sized to fit within the cavity and defining openings configuredfor holding a plurality of sample vessels and having sidewallsconfigured to be in contact with sidewalls of the sample vessels,wherein vessels are arranged such that each patient has at least a firstsample with a first anticoagulant and a second sample with a secondanticoagulant in the matrix.

In another embodiment described herein, a thermal-controlled transportcontainer is provided for use in shipping a plurality of sample vessels,the transport container comprising: a) a bottom container portioncomprising a bottom wall and at least a first sidewall defining a cavityadapted to contain a product therein; b) a top container portioncomprising a top surface and a bottom surface and adapted to combinewith said bottom container portion to define a product cavity, said topcontainer portion forming a top wall for said vessel; wherein at leastone of said top, bottom and side walls comprises a phase changematerial.

In another embodiment described herein, a thermal-controlled transportcontainer is provided for use in shipping a plurality of sample vessels,the transport container comprising: a) a bottom container portioncomprising a bottom wall and at least a first sidewall defining a cavityadapted to contain a product therein; b) a top container portioncomprising a top surface and a bottom surface and adapted to combinewith said bottom container portion to define a product cavity, said topcontainer portion forming a top wall for said vessel; c) a holder fordefining a plurality of sample vessel holding spaces to position thesample vessels in a pre-determined orientation; wherein at least one ofsaid top, bottom and side walls comprises a phase change material.

In another embodiment described herein, a transport container isprovided for shipping sample vessels, the container comprising: agenerally rectangular floor; generally parallel sides projecting fromlongitudinal edges of the floor; generally parallel ends projecting fromend edges of the floor and bridging the sides; a cover fittable over thesides and ends and forming therewith and with the floor a generallyclosed space; a sample vessel holder removably coupled to the floor inan interior of the container and configured to define vessel-holdingspaces. Optionally, the vessel holding spaces are configured to holdair-evacuated blood collection tubes having an interior volume of about2 ml or less. In at least one embodiment, the vessel holding spaces areconfigured to hold vessels such as but not limited to air-evacuatedcollection tubes having an interior volume of about 1 ml, or less thanabout 500 or less than about 250 or less than about 100 or less thanabout 50 or less.

In another embodiment described herein, a thermal-controlled transportcontainer is provided for use in shipping a plurality of sample vessels,the transport container comprising: means for holding a plurality ofsample vessels in at least one fixed orientation; means for thermallycontrolling temperature of the sample vessels to be within a desiredrange of about 0° C. to 10° C.; wherein the means from holding theplurality of sample vessels is removable from the transport container.Optionally, the vessel holding spaces are configured to holdair-evacuated blood collection tubes having an interior volume of about2 ml or less. In embodiments, the vessel holding spaces are configuredto hold air-evacuated collection tubes having an interior volume ofabout 1 ml, or less than about 500 or less than about 250 or less thanabout 100 or less than about 50 or less.

It should be understood that some embodiments may comprise a kit thatincludes a transport container as recited in any of the above.Optionally, the kit includes a transport container and instructions fortheir use.

In one embodiment described herein, a method is described for providinga whole blood sample and/or partition thereof from a sender to arecipient. The method comprises transporting a package comprising asample vessel comprising one or more channels that contains (a) a wholeblood sample and/or partition thereof in fluid state having a volumeless than or equal to about 200 microliters (ul) and (b) one or morereagents used for preserving one or more analytes in the whole bloodsample and/or partition thereof for analysis until at least when wholeblood sample and/or partition thereof reaches the recipient, and whereinthe depositing results in delivery of the sample vessel to therecipient. By way of non-limiting example, transporting the samplevessel may occur by using a parcel delivery service, a courier, or othershipping service.

In one embodiment described herein, a method is described for preparinga whole blood sample for delivery to a sample processing station. Themethod comprises depositing a sample vessel having a whole blood samplein fluid state and a volume less than or equal to about 200 μL with adelivery service for delivering the sample vessel to the sampleprocessing location for processing the whole blood sample. The samplevessel may be prepared by (a) drawing the whole blood sample from asubject with the aid of a capillary channel and (b) placing the wholeblood sample into the sample vessel, wherein the whole blood sample ispreserved in fluid state with one or more reagents contained in thecapillary channel and/or the sample vessel.

It should be understood that any of the embodiments herein may beadapted to have one or more of the following features. By way ofnon-limiting example, the sample in some embodiments may be a semi-solidor gel state. This may occur after the sample is in the sample vessel.Optionally, the delivery service is a mail delivery service. Optionally,the blood sample is collected from the subject at a point of carelocation. Optionally, the point of care location is a home of thesubject. Optionally, the point of a care location is the location of ahealthcare provider.

In another embodiment described herein, a method for processing a wholeblood sample comprises receiving at a processing station from a parceldelivery service, a sample vessel having a whole blood sample less thanor equal to about 200 μL, wherein the sample vessel is received at theprocessing station with the whole blood sample in a fluid state; andperforming, at the processing station, at least one pre-analyticaland/or analytical assay on the whole blood sample in a fluid state.

It should be understood that any of the embodiments herein may beadapted to have one or more of the following features. By way ofnon-limiting example, the assay has one or more steps. Optionally, thesample vessel is included in a housing having one or more environmentalcontrol zones. Optionally, the housing is adapted to control a humidityof each of the environmental control zones. Optionally, the housing isadapted to control a pressure of each of the environmental controlzones.

In yet another embodiment described herein, a computer-implementedmethod is provided for queuing a blood sample for processing at aprocessing location. The method comprises (a) identifying, with the aidof a geolocation system having a computer processor, the geolocation ofa transport container having the blood or other bodily fluid sample; (b)estimating, with the aid of a computer processor, delivery time of thetransport container to the processing location; and (c) based on theestimated time of delivery, providing a notification for preparativework for processing the sample at the processing location.

In yet another embodiment described herein, a method is described forpreparing a whole blood sample for delivery to a sample processingstation. The method comprises depositing a sample vessel having a wholeblood sample in fluid state with a delivery service for delivering thesample vessel to the sample processing location for processing the wholeblood sample, wherein the sample vessel is prepared by (a) drawing thewhole blood sample from a subject using a device and (b) placing thewhole blood sample into the sample vessel.

Optionally, depositing may encompass pick-up and/or drop-off of a samplevessel. Optionally, processing may include pre-analytic, analytic andpost-analytic processing of a sample. Optionally, delivery service mayinclude a subject's delivery service or a third party delivery service.Optionally, the whole blood sample is preserved in fluid state with oneor more reagents contained in the capillary channel or the samplevessel.

In yet another embodiment described herein, a method is provided forprocessing a whole blood sample at a processing station. The methodcomprises receiving, at the processing station from a delivery service,a sample vessel having a whole blood sample, wherein the sample vesselis prepared by (a) drawing the whole blood sample from a subject using acollection device and (b) placing the whole blood sample into the samplevessel. The method also includes performing, at the processing station,at least one pre-analytical or analytic assay on the whole blood sample.

It should be understood that any of the embodiments herein may beadapted to have one or more of the following features. By way ofnon-limiting example, with the aid of a computer processor, providing atime for completion of the processing from the estimated time ofdelivery. Optionally, the method includes queuing the sample vessel forprocessing upon estimating the time of delivery of the sample vessel atthe processing location. Optionally, the geolocation of the samplevessel is identified with the aid of a communications network.

In one embodiment described herein, a computer-implemented method isdescribed for providing an estimated time of completion for theprocessing of a blood sample. The method comprises receiving informationabout a transport container transported through a delivery service to aprocessing station that is for sample processing, the transportcontainer having a blood sample removed from a subject. The method alsoincludes calculating, with the aid of a computer processor, a positionof the blood sample in a processing queue at the processing station,wherein the predicting is based on (i) information about the position ofblood or other bodily fluid samples from other subjects in theprocessing queue and (ii) information about the geographic location ofother sample vessels having blood samples from other subjects inrelation to the sample vessel having the blood sample removed from thesubject. The method includes predicting a time for processing the bloodsample at the processing station upon delivery of the sample vessel bythe delivery service to the processing station; and based on thepredicting and an estimated time of delivery of the sample vessel to theprocessing station, providing the subject or a healthcare providerassociated with the subject an estimated time for processing the bloodsample from the subject, the estimated time measured from the point thesample vessel is deposited with the delivery service. Optionally, thesample is transported to a plurality of processing stations. It shouldbe understood that processing as used herein is to be broadlyinterpreted and may include pre-analytical, analytical, and/orpost-analytical step(s).

In yet another embodiment described herein, a computer-implementedmethod is described for providing an estimated time of completion forthe processing of a blood sample from a subject. The method comprisesreceiving information about a transport container transported through adelivery service to a processing station that is for sample processing,the transport container having at least one blood or bodily fluid sampleremoved from the subject. The method also includes calculating, with theaid of a computer processor, a position of the blood sample in aprocessing queue at the processing station, wherein the predicting isbased on (i) information about the position of blood samples from othersubjects in the processing queue and (ii) information about thegeographic location of other sample vessels having blood samples fromother subjects in relation to the transport container having the bloodsample removed from the subject. The method includes predicting a timefor processing the blood sample at the processing station upon deliveryof the transport container by the delivery service to the processingstation; and based on the predicting and an estimated time of deliveryof the transport container to the processing station, allocating one ormore resources at the processing station for processing the blood sampleupon delivery to the processing station.

It should be understood that any of the embodiments herein may beadapted to have one or more of the following features. By way ofnon-limiting example, the transport container has an information storageunit that allows identification of the transport container by thedelivery service and/or the processing location. Optionally, theinformation storage unit is a radiofrequency identification (RFID) tag.Optionally, the information storage unit is a barcode. Optionally, theinformation storage unit is a microchip. Optionally, the transportcontainer comprises one or more sensors for collecting one or more ofthe temperature of the bodily fluid sample (e.g., a blood sample), thepressure of the sample vessel, the pH of the sample, the turbidity ofthe sample, the viscosity of the sample, or other characteristic of thesample. Optionally, the processing location processes collected bodilyfluid samples on an on-demand basis. Optionally, the transport containerincludes a geo-location device for providing the location of the samplevessel. Optionally, the anti-coagulating agent is selected from thegroup consisting of heparin, ethylenediaminetetraacetic acid, ananti-coagulant, or other additive. Optionally, the transport container,wherein the container holding spaces are configured to holdair-evacuated blood collection tubes, are configured to holdair-evacuated sample collection tubes having a partial vacuum of at mostabout 30% vacuum, or at most about 40% vacuum, or at most about 50%vacuum, or at most about 60% vacuum, or at most about 70% vacuum, or atmost about 80% vacuum, or at most about 90% vacuum.

In embodiments described herein involving a first vessel and a secondvessel, in certain embodiments, the interior volume of the first vesseland second vessel is each 1000, 750, 500, 400, 300, 250, 200, 150, 100,90, 80, 70, 60, 50, 40, 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2microliters, or less. In embodiments described herein involving a firstvessel and a second vessel, in certain embodiments, the interior volumeof neither the first vessel nor the second vessel exceeds 1000, 750,500, 400, 300, 250, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 25, 20,15, 10, 9, 8, 7, 6, 5, 4, 3, or 2 microliters. In embodiments describedherein involving one or more vessels, in certain embodiments, theinterior volume of each of the one or more vessels is 1000, 750, 500,400, 300, 250, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 25, 20, 15,10, 9, 8, 7, 6, 5, 4, 3, 2 microliters, or less. In embodimentsdescribed herein involving one or more vessels, in certain embodiments,the interior volume of none of the one or more vessels exceeds 1000,750, 500, 400, 300, 250, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 25,20, 15, 10, 9, 8, 7, 6, 5, 4, 3, or 2 microliters.

In embodiments described herein involving a first vessel and a secondvessel, each containing a portion of a small volume bodily fluid sample,in certain embodiments, neither the first vessel nor the second vesselcontains a portion of the small volume bodily fluid sample having avolume of greater than 500, 400, 300, 250, 200, 150, 100, 90, 80, 70,60, 50, 40, 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, or 2 microliters.

In embodiments described herein involving a vessel containing a smallvolume bodily fluid sample, in certain embodiments, the volume of thesmall volume bodily fluid sample in the vessel is no greater than 500,400, 300, 250, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 25, 20, 15,10, 9, 8, 7, 6, 5, 4, 3, or 2 microliters.

In embodiments described herein involving one or more vessels containingbodily fluid sample, in certain embodiments, at least one of the one ormore vessels contains bodily fluid sample which fills at least 99, 98,97, 96, 95, 90, 85, 80, 75, 70, 60, 50, 40, 30, 20, 10, or 5% of theinterior volume of the vessel. In embodiments described herein involvingone or more vessels containing bodily fluid sample, in certainembodiments, all of the one or more vessels contains bodily fluid samplewhich fills at least 99, 98, 97, 96, 95, 90, 85, 80, 75, 70, 60, 50, 40,30, 20, 10, or 5% of the interior volume of the vessel.

In embodiments described herein involving a sample collection site and asample receiving site, in embodiments, the sample collection site andsample receiving site may be in the same room, building, campus, orcollection of buildings. In embodiments described herein involving asample collection site and a sample receiving site, in embodiments, thesample collection site and sample receiving site may be in differentrooms, buildings, campuses, or collection of buildings. In embodiments,a sample collection site and a sample receiving site may be separated byat least 1 meter, 5 meters, 10 meters, 50 meters, 100 meters, 500meters, 1 kilometer, 5 kilometers, 10 kilometers, 15 kilometers, 20kilometers, 30 kilometers, 50 kilometers, 100 kilometers, or 500kilometers. In embodiments, a sample collection site and samplereceiving site may be separated by no more than 5 meters, 10 meters, 50meters, 100 meters, 500 meters, 1 kilometer, 5 kilometers, 10kilometers, 15 kilometers, 20 kilometers, 30 kilometers, 50 kilometers,100 kilometers, 500 kilometers, or 1000 kilometers. In embodiments, asample collection site and a sample receiving site may be separated byat least 1 meter, 5 meters, 10 meters, 50 meters, 100 meters, 500meters, 1 kilometer, 5 kilometers, 10 kilometers, 15 kilometers, 20kilometers, 30 kilometers, 50 kilometers, 100 kilometers, or 500kilometers and no more than 5 meters, 10 meters, 50 meters, 100 meters,500 meters, 1 kilometer, 5 kilometers, 10 kilometers, 15 kilometers, 20kilometers, 30 kilometers, 50 kilometers, 100 kilometers, 500kilometers, or 1000 kilometers. In embodiments, a first locationdescribed herein may be a sample collection site and a second locationdescribed herein may be a sample receiving site.

In embodiments described herein involving a vessel containing at least aportion of a small volume bodily fluid sample being transported from asample collection site to a sample receiving site, in embodiments, thebodily fluid sample may be maintained in liquid form during thetransport of the vessel. In embodiments described herein involving twoor more vessels, each containing at least a portion of a small volumebodily fluid sample, being transported from a sample collection site toa sample receiving site, in embodiments, the bodily fluid sample in eachof the vessels may be maintained in liquid form during the transport ofthe vessels.

In embodiments described herein involving one or more vessels beingtransported from a sample collection site to a sample receiving site, inembodiments, the one or more vessels may be transported in a transportcontainer. In embodiments described herein involving one or more vesselsbeing transported in a transport container, in embodiments, the one ormore vessels may be positioned in an array in the transport container,and the array may contain at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15,20, 25, 30, 35, 40, 50, or 100 vessels per square inch, when viewed fromthe top down.

In embodiments described herein involving transporting one or morevessels in a transport container, in embodiments, the transportcontainer may contain bodily fluid samples from at least 1, 2, 3, 4, 5,6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 50, or 100 different subjects.

In embodiments described herein involving a vessel containing at least aportion of a bodily fluid sample, in embodiments, the vessel may containan anticoagulant. In embodiments involving two or more vessels whicheach contain a portion of a bodily fluid sample from a subject, inembodiments, at least one or all of the vessels may contain ananticoagulant. In embodiments, when two or more vessels which eachcontain a portion of a bodily fluid sample from a subject also eachcontain an anticoagulant, the vessels may contain the sameanticoagulants or different anticoagulants. An anticoagulant in a vesselmay be, for example, heparin or EDTA.

In methods described herein involving the transport of a bodily fluidsample in one or more vessels from a sample collection site to a samplereceiving site, in embodiments, the bodily fluid sample may arrive atthe sample receiving site no more than 48 hours, 36 hours, 24 hours, 16hours, 12 hours, 8 hours, 7 hours, 6 hours, 5 hours, 4 hours, 3 hours, 2hours, 60 minutes, 45 minutes, 30 minutes, 20 minutes, 15 minutes, 10minutes, or 5 minutes after the bodily fluid sample was obtained fromthe subject.

In methods described herein involving transporting at least a vesselfrom a sample collection site to a sample receiving site, inembodiments, the method may further comprise centrifuging the vesselbefore it is transported. In methods described herein involvingtransporting a plurality of vessels from a sample collection site to asample receiving site, in embodiments, the method may further comprisecentrifuging the plurality of vessels before they are transported.

In methods described herein involving transporting at least a firstvessel from a sample collection site to a sample receiving site, inembodiments, at the sample receiving site and prior to the removal ofsample from the first vessel, the first vessel is inserted into a sampleprocessing device comprising an automated fluid handling apparatus. Inmethods described herein involving transporting at least a first vesseland a second vessel from a sample collection site to a sample receivingsite, in embodiments, at the sample receiving site and prior to theremoval of sample from the first vessel, the first vessel and secondvessel are inserted into a sample processing device comprising anautomated fluid handling apparatus. In embodiments, when a vesselcomprising a sample is inserted into a sample processing devicecomprising an automated fluid handling apparatus, sample may be removedfrom the vessel by the automated fluid handling apparatus. Inembodiments, prior to the insertion of a vessel comprising a sample intoa sample processing device comprising an automated fluid handlingapparatus, the vessel is inserted into a cartridge, and the cartridge isthen inserted into the sample processing device. A cartridge mayaccommodate any number of vessels containing sample, such as at least 1,2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 50, or 100 vessels. A cartridgemay further comprise one or more reagents for performing one or morelaboratory tests with the sample. In embodiments, a cartridge maycomprise all of the reagents necessary to perform all of the tests thatare to be performed with the sample(s) in the cartridge.

In embodiments, a portion of a portion of a bodily fluid sample of avessel may be of any amount. For example, in embodiments, a portion of aportion of a bodily fluid sample of a first vessel may be a portion of afirst vessel original sample or a portion of a first vessel dilutionsample. In another example, in embodiments, a portion of a portion of abodily fluid sample of a second vessel may be a portion of a secondvessel original sample or a portion of a second vessel dilution sample.

In embodiments provided herein involving transporting one or morevessels, each containing at least a portion of a bodily fluid samplefrom a sample collection site to a sample receiving site, inembodiments, one or more steps of any number of laboratory tests may beperformed with a portion of the at least a portion of the bodily fluidsample in the vessel. For example, in embodiments, one or more steps of1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90,100, 200, 300, 400, 500, or 1000 or more different laboratory tests maybe performed with a portion of the at least a portion of bodily fluidsample. Each different laboratory test may use a separate portion of thebodily fluid sample, or in embodiments, more than one differentlaboratory test may be performed with a particular portion of the bodilyfluid sample. The different laboratory tests may be of the same type,different types, or a mixture of same and different types. The one ormore vessels may be, for example, a first vessel or a first vessel andsecond vessel.

In embodiments, when a bodily fluid sample from a subject transportedaccording to systems or methods provide herein is used for more than onelaboratory test, each of the laboratory tests may use the equivalent ofno more than 50, 40, 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0.5,0.1, 0.05, or 0.01 of neat bodily fluid sample (e.g. undiluted wholeblood, saliva, or urine) per test.

In embodiments provided herein involving obtaining at a samplecollection site a plurality of vessels collectively containing a smallvolume bodily fluid sample from a subject, in embodiments, the totalvolume of the small volume bodily fluid sample obtained from the subjectbetween all of the vessels of the plurality of vessels may be no greaterthan 500, 400, 300, 250, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 25,20, 15, 10, 9, 8, 7, 6, 5, 4, 3, or 2 microliters.

In embodiments provided herein involving transporting a vesselcontaining at least a portion of a bodily fluid sample from a samplecollection site to a sample receiving site, removing at the samplereceiving site from the vessel an original sample, and then generating adilution sample from the original sample, in embodiments, the dilutionmay be generated step-wise or serially. In embodiments, the dilutionsample may have a total volume of no more than 1000, 900, 800, 700, 600,500, 400, 300, 250, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 25, 20,15, 10, 9, 8, 7, 6, 5, 4, 3, or 2 microliters. In embodiments, thedilution sample may be diluted at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15,20, 50, 100, 200, 300, 400, 500, 1000, 5,000, 10,000, 50,000, or100,000-fold relative to the original sample.

In embodiments provided herein involving transporting at least a firstvessel and a second vessel, each containing a portion of the smallvolume bodily fluid sample obtained from the subject, from a samplecollection site to a sample receiving site, in embodiments, at thesample receiving site, a first vessel original sample may be removedfrom the first vessel and a second vessel original sample may be removedfrom the second vessel. From the first vessel original sample a firstvessel dilution sample may be generated. From the second vessel originalsample a second vessel dilution sample may be generated. The firstvessel dilution sample and second vessel dilution samples may have thesame or different volumes and degrees of dilution. In embodiments,multiple different dilution samples may be generated from one or both ofthe first vessel original sample or second vessel original sample. Thedifferent dilution samples may be used for one or more differentlaboratory tests, which may be of different types. In embodiments, afirst vessel dilution sample may be diluted at least 2, 3, 4, 5, 6, 7,8, 9, 10, 15, 20, 50, 100, 200, 300, 400, 500, 1000, 5,000, 10,000,50,000, or 100,000-fold relative to the first vessel original sample andhave a total volume of no more than 1000, 900, 800, 700, 600, 500, 400,300, 250, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 25, 20, 15, 10, 9,8, 7, 6, 5, 4, 3, or 2 microliters, and a second vessel dilution samplemay be diluted at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 50, 100,200, 300, 400, 500, 1000, 5,000, 10,000, 50,000, or 100,000-foldrelative to the second vessel original sample and have a total volume ofno more than 1000, 900, 800, 700, 600, 500, 400, 300, 250, 200, 150,100, 90, 80, 70, 60, 50, 40, 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, or2 microliters.

In embodiments provided herein involving obtaining at a samplecollection site a vessel, the vessel containing a small volume bodilyfluid sample obtained from a subject, in embodiments, volume of thesmall volume bodily fluid sample in the vessel may be no greater than500, 400, 300, 250, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 25, 20,15, 10, 9, 8, 7, 6, 5, 4, 3, or 2 microliters.

In embodiments provided herein involving obtaining at a samplecollection site a vessel, the vessel containing a small volume bodilyfluid sample obtained from a subject and transporting the vessel fromthe sample collection site to a sample receiving site, in embodiments,the small volume bodily fluid sample may be divided into any number ofportions, such as, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40, 50,60, 70, 80, 90, 100, 200, 300, 400, 500, or 1000 different portions. Theportions may be diluted in the same or in varying amounts, and may beused for, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30,40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, or 1000 or moredifferent laboratory tests.

In embodiments provided herein involving obtaining at a samplecollection site at least a vessel containing at least a portion of asmall volume bodily fluid sample from a subject, in embodiments, theobtaining step may include collecting the small volume bodily fluidsample from the subject (e.g. from a fingerstick or venous draw).

In embodiments provided herein involving performing at least a portionof a laboratory test in an assay unit, in embodiments, the assay unitmaybe movable, such as by a fluid handling apparatus. In embodimentsincluding two or more assay units, in embodiments, the assay units maybe independently movable.

In embodiments provided herein involving transport of one or morevessels containing a bodily fluid sample, in some embodiments, thevessels may have any of the characteristics of vessels described herein,or of other vessels suitable for the storage of bodily fluids. In someembodiments, the vessels may be loaded with bodily fluid sample by anyof the devices or methods provided herein, or by other suitabletechniques for loading a vessel have a small interior volume. Forexample, in certain embodiments, a vessel to be transported according toa system or method provided herein may be loaded with a sample by asyringe or a pipette tip.

Optionally, at least one embodiment of a sample collection device hereincan separate a single blood sample into different vessels for differentpre-analytical processing. This can be achieved through fluid pathwaysin the device and/or through different inlet ports on the device.

In at least another embodiment described herein, a method is providedfor use with a bodily fluid sample from a subject, the methodcomprising: shipping a plurality of sample containers from a firstlocation to a second location, wherein each of said sample containerscontains a sample of about 500 μL or less and wherein interior volume ofeach of the sample containers is about 600 μL or less, wherein shippingof the plurality of samples containers is accomplished using a firstframe sized to fit in a shipping container, said first frame comprises aplurality of openings each sized and shaped to engage at least one ofthe sample containers and hold the sample containers in a desiredorientation; obtaining data from each of the sample containers;providing a plurality of processing frames at the second location; usingsaid data from the sample containers to determine which of saidprocessing frames receive which of said sample containers; and movingsaid sample containers from the shipping frame to the processing framebased on data provided by the sample containers and based on sortinginformation; and handling the processing frame to simultaneously processthe sample containers processing frame.

Optionally, obtaining data comprises simultaneously scanning a pluralityof sample container IDs simultaneously. Optionally, scanning occurs whenthe containers are in the shipping frame. Optionally, scanning comprisesscanning an underside surface of the shipping containers. Optionally,determining which processing frames receive which of the samplecontainers comprises referencing the data with at least one database ata server. Optionally, determining comprises matching container ID withsubject ID. Optionally, determining comprises matching container ID withpre-processing procedure. Optionally, at least some of the samplecontainers contain sample having a first anticoagulant and at least someother of the sample containers have a second, different anticoagulant.

In one embodiment, a method for use with a bodily fluid sample from asubject, the method comprising: shipping a plurality of samplecontainers from a first location to a second location, wherein each ofsaid sample containers contains about 500 μL or less but greater thanabout 30 μL of the bodily fluid sample, wherein interior volume of eachof the sample containers is about 600 μL or less, subjecting the bodilyfluid sample to a first accelerated sedimentation force of at leastabout 1400 g or greater to form a first processed sample; shipping thefirst processed sample from a first location to a second location; andsubjecting the first processed sample at the second location to a secondaccelerated sedimentation force of greater than about 10 g but less thanabout 500 g.

Any of the embodiments herein may be configured to one or more of thefollowing features. In one embodiment, the first processed samplecontains a first anti-coagulant. Optionally, the first processed samplecontains a heparin-based anti-coagulant. Optionally, the first processedsample contains a plasma portion separated by a separation gel from aformed-blood component portion. Optionally, the second processed sampledoes not force electrolytes though the separation gel from theformed-blood component portion to the plasma portion. Optionally, thesecond processed sample does not force liquid though the separation gelfrom the formed-blood component portion to the plasma portion.Optionally, the first accelerated sedimentation force is providedthrough centrifugation. Optionally, the second accelerated sedimentationforce is provided through centrifugation. Optionally, a plurality ofsamples are shipped from a first location to a second location, whereineach of said samples undergoes a first accelerated sedimentation on anindividual basis and wherein said plurality of samples undergoes asecond accelerated sedimentation simultaneously as a group. Optionally,a plurality of samples are shipped from a first location to a secondlocation, wherein each of said samples undergoes a first acceleratedsedimentation on an individual basis and wherein said plurality ofsamples undergoes a second accelerated sedimentation simultaneously as agroup in a single tray. Optionally, a plurality of samples are shippedfrom a first location to a second location, wherein each of said samplesundergoes a first accelerated sedimentation on an individual basis andwherein said plurality of samples undergoes a second acceleratedsedimentation simultaneously as a group in at least one tray on a traycentrifuge.

Optionally, a dead volume about the sample in each of the samplecontainers containing sample is about 60 uL or less. Optionally, a deadvolume about the sample in each of the sample containers containingsample is about 50 uL or less Optionally, a dead volume about the samplein each of the sample containers containing sample is about 40 uL orless. Optionally, a dead volume about the sample in each of the samplecontainers containing sample is about 30 uL or less. Optionally, a deadvolume about the sample in each of the sample containers containingsample is about 20 uL or less. Optionally, dead volume about the samplein each of the sample containers containing sample is about 10 uL orless. Optionally, at least some of the sample containers contain samplehaving a first anticoagulant and at least some other of the samplecontainers have a second, different anticoagulant.

Any of the embodiments herein may be configured to one or more of thefollowing features. In one embodiment, the method comprises collectingcapillary blood from a subject, the blood is collected in a plurality ofvessels, wherein no more than 500 microliters per vessel but greaterthan at least about 10 microliters per vessel. Optionally, whole bloodis collected in a plurality of vessels, wherein no more than 400microliters per vessel but greater than at least about 10 microlitersper vessel. Optionally, whole blood is collected in a plurality ofvessels, wherein no more than 300 microliters per vessel but greaterthan at least about 10 microliters per vessel. Optionally, the wholeblood is collected in a plurality of vessels, wherein no more than 200microliters per vessel but greater than at least about 10 microlitersper vessel. Optionally, blood is collected in a plurality of vessels,wherein no more than 100 microliters per vessel but greater than atleast about 10 microliters per vessel. Optionally, a method is providedcomprising shipping a fluid sample in liquid form from a first locationto a second location. Optionally, the method comprises shipping a fluidsample in liquid form from a first location to a second locationcomprising centrifuging the sample to at least 1500 g at the firstlocation and not more than 400 g but greater than 10 g at the secondlocation. Optionally, the method comprises shipping a fluid sample inliquid form from a first location to a second location comprisingapplying a first accelerated sedimentation force such as but not limitedto centrifuging the sample to at least 1400 g at the first location andnot more than 500 g but greater than 10 g at the second location.Optionally, the method comprises shipping a fluid sample in liquid formfrom a first location to a second location comprising centrifuging thesample to at least 1500 g at the first location and not more than 400 gbut greater than 10 g at the second location, wherein the sample isbetween about 50 to about 200 microliters. Optionally, the methodcomprises shipping a fluid sample in liquid form from a first locationto a second location comprising centrifuging the sample to at least 1500g at the first location and not more than 400 g but greater than 10 g atthe second location, wherein the sample is between about 50 to about 300microliters. Optionally, the method comprises shipping a fluid sample inliquid form from a first location to a second location comprisingcentrifuging the sample to at least 1500 g at the first location and notmore than 400 g but greater than 10 g at the second location, whereinthe sample is between about 20 to about 180 microliters. Optionally, themethod comprises shipping a fluid sample in liquid form from a firstlocation to a second location comprising centrifuging the sample to atleast 1500 g at the first location and not more than 400 g but greaterthan 10 g at the second location, wherein the sample is between about 20to about 200 microliters, in a vessel with a dead volume of about 5 toabout 30 microliters when filled with said sample. Optionally, a devicecomprising a transport container is provided. Optionally, the methodcomprises shipping a fluid sample in liquid form from a first locationto a second location comprising centrifuging the sample to at least 1400g at the first location and not more than 500 g at the second location.Optionally, a system is provided comprising a processor programmed todetermine at least a desired sample dilution for a sample and at least adesired number of aliquot(s).

In embodiments, provided herein is a device comprising: a channelcomprising an anticoagulant coating; and a vessel configured to be influid communication with the channel, wherein the device is configuredto: receive, in the channel, a bodily fluid sample provided by asubject; mix, in the channel, the bodily fluid sample with theanticoagulant coating to generate a mixed bodily fluid sample based on afluid flow of at least a portion of the bodily fluid sample across theanticoagulant coating; and collect, in the vessel, the mixed bodilyfluid sample, wherein the anticoagulant coating comprises EDTA, andwherein the mixed bodily fluid sample comprises a bulk concentration ofEDTA no less than about 2.5 milligrams per milliliter and no greaterthan about 10 milligrams per milliliter. In embodiments, the bulkconcentration of EDTA is no less than about 2.5 milligrams permilliliter and no greater than about 15 milligrams per milliliter in themixed bodily fluid sample. In embodiments, the bulk concentration ofEDTA is no less than about 2.5 milligrams per milliliter and no greaterthan about 20 milligrams per milliliter in the mixed bodily fluidsample. In embodiments, the bulk concentration of EDTA is no less thanabout 3 milligrams per milliliter and no greater than about 4 milligramsper milliliter in the mixed bodily fluid sample. In embodiments, thebulk concentration of EDTA is no less than about 2.5 milligrams permilliliter and no greater than about 4 milligrams per milliliter in themixed bodily fluid sample. In embodiments, the bulk concentration ofEDTA is no less than about 2.5 milligrams per milliliter and no greaterthan about 5 milligrams per milliliter in the mixed bodily fluid sample.In embodiments, the bulk concentration of EDTA is no less than about 2.5milligrams per milliliter and no greater than about 6 milligrams permilliliter the mixed bodily fluid sample. In embodiments, the bulkconcentration of EDTA in the final sample is no less than about 2.15milligrams per milliliter and no greater than about 4 milligrams permilliliter the mixed bodily fluid sample.

Optionally, this concentration may be achieved in one embodiment bycoating a chamber or capillary tube of a known volume with an EDTAsolution that is dried onto the walls in a sufficient amount so thatsufficient EDTA is on the walls to achieve the desired EDTAconcentration for a sample volume equal to the known volume (andassuming all 100% of the dried EDTA will mix with the sample).Optionally, another embodiment may approach this by coating a chamber orcapillary tube of a known volume with an EDTA solution that is driedonto the walls in a sufficient amount so that sufficient EDTA is on thewalls to achieve the desired EDTA concentration for a sample volumeequal to the known volume (and adjusting the amount of EDTA based onabout a 60 to about 90 second time of the sample with the EDTA, asmeasured from when the sample begins to fill the chamber or capillary).Optionally, this may be achieved in one embodiment by coating a chamberor capillary tube of a known volume with dried EDTA in a sufficientamount so that sufficient EDTA is on the walls to achieve the desiredEDTA concentration for a sample amount equal to the known volume,assuming that about 60% to 75% of the EDTA on the walls will mix withthe sample during the 60 to 90 seconds that the sample is in contactwith the EDTA. In embodiments, the device is configured to mix thebodily fluid sample with the anticoagulant with a shear rate no greaterthan about 1,000 reciprocal seconds.

Optionally, the amount of EDTA coated on the walls maybe adjusted toaccount for about 60% to 75% of the amount mixing with the sample. Inone non-limiting example, an amount sufficient for about 4.7 mg/mL maybe coated on the walls, but the concentration in the final sample may beabout 3.5 mg/mL based on the 60% to 75% of the EDTA entering the sample.Optionally, longer exposure times could increase the range so that morethan 75% of the EDTA mixes with the sample. Optionally, longer exposuretimes could increase the range so that between about 65 to about 80% ofthe EDTA mixes with the sample. Optionally, longer exposure times couldincrease the range so that between about 70 to about 85% of the EDTAmixes with the sample. Optionally, longer exposure times could increasethe range so that more than 90% of the EDTA mixes with the sample.Optionally, these coating amounts may be applicable to any of theembodiments described or suggested in this application.

In embodiments, the device is further configured to mix the bodily fluidsample with the anticoagulant without generating a local concentrationof EDTA greater than about 10, 15, 20, 25, 30, 35, 40, 45, or 50milligrams per milliliter. In embodiments, the device is furtherconfigured to mix the bodily fluid sample with the anticoagulant with ashear rate no greater than about 1,000 reciprocal seconds. Inembodiments, the channel of the device comprises a hydraulic diameter noless than about 0.5 millimeters and no greater than about 10millimeters. In embodiments, the channel of the device comprises amixing element, and wherein the device is further configured to mix, inthe channel, the bodily fluid sample with the anticoagulant coatingbased on an advection. In embodiments, a concentration of theanticoagulant coating varies along a length of the channel according toa gradient. In embodiments, a magnitude of the gradient of theanticoagulant concentration decreases as the distance from an open endof the channel increases. In embodiments, a thickness of theanticoagulant coating varies along a length of the channel according toa gradient. In embodiments, a magnitude of the gradient of theanticoagulant thickness decreases as the distance from an open end ofthe channel increases.

In embodiments provided herein comprising a mixing element in a channel,the mixing element may comprise a protrusion on a surface of thechannel. Optionally, the mixing element may comprise a staggeredherringbone structure on a surface of the channel.

In embodiments, a bodily fluid sample prepared in a device, system, ormethod as provided herein may contain a concentration of EDTA of atleast 0.1, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, or 10 mgEDTA/ml, of no more than 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7,8, 9, 10, 15, or 20 mg EDTA/ml, or of at least 0.1, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, or 10 mg EDTA/ml and no more than 0.5, 1,1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 15, or 20 mg EDTA/ml.

In embodiments, provided herein is a device comprising: a channelcomprising an anticoagulant coating; and a vessel configured to be influid communication with the channel, wherein the device is configuredto: receive, in the channel, a bodily fluid sample provided by asubject; mix, in the channel, the bodily fluid sample with theanticoagulant coating to generate a mixed bodily fluid sample based on afluid flow of at least a portion of the bodily fluid sample across theanticoagulant coating; and collect, in the vessel, the mixed bodilyfluid sample, wherein the anticoagulant coating comprises heparin, andwherein the mixed bodily fluid sample comprises a bulk concentration ofheparin no less than about 20 units per milliliter and no greater thanabout 150 units per milliliter. In embodiments, the bulk concentrationof heparin is no less than about 30 units per milliliter and no greaterthan about 50 units per milliliter. In embodiments, the device isfurther configured to mix the bodily fluid sample with the anticoagulantwith a shear rate no greater than about 1,000 reciprocal seconds. Inembodiments, the channel comprises a hydraulic diameter no less thanabout 0.5 millimeters and no greater than about 10 millimeters. Inembodiments, the channel comprises a mixing element, and the device isfurther configured to mix, in the channel, the bodily fluid sample withthe anticoagulant coating based on an advection. In embodiments, aconcentration of the anticoagulant coating varies along a length of thechannel according to a gradient. In embodiments, a magnitude of thegradient of the anticoagulant concentration decreases as the distancefrom an open end of the channel increases. In embodiments, a thicknessof the anticoagulant coating varies along a length of the channelaccording to a gradient. In embodiments, a magnitude of the gradient ofthe anticoagulant thickness decreases as the distance from an open endof the channel increases.

In embodiments, a bodily fluid sample prepared in a device, system, ormethod as provided herein may contain a concentration of heparin of atleast 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19,20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140,150, 200, or 250 units heparin/ml, of no more than 2, 3, 4, 5, 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50,60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 200, 250, 300, 350, 400,or 500 units heparin/ml, or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80,90, 100, 110, 120, 130, 140, 150, 200, or 250 units heparin/ml and nomore than 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18,19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140,150, 200, 250, 300, 350, 400, or 500 units heparin/ml.

In embodiments, provided herein is a method comprising: receiving, in achannel, a bodily fluid sample provided by a subject; mixing the bodilyfluid sample with an anticoagulant to generate a mixed bodily fluidsample; and collecting, in a vessel in fluid communication with thechannel, the mixed bodily fluid sample, wherein the anticoagulantcomprises EDTA, and wherein the mixed bodily fluid sample comprises abulk concentration of EDTA no less than about 2.5 milligrams permilliliter and no greater than about 10 milligrams per milliliter. Inembodiments, mixing the bodily fluid sample with the anticoagulantcomprises mixing the bodily fluid sample with the anticoagulant withoutgenerating a local concentration of EDTA greater than about 20milligrams per milliliter. In embodiments, the mixed bodily fluid samplereaches the bulk concentration of EDTA at a time less than 90 secondsafter the bodily fluid sample was initially received in the channel. Inembodiments, mixing the bodily fluid sample with the anticoagulantcomprises mixing the bodily fluid sample with the anticoagulant with ashear rate no greater than about 1,000 reciprocal seconds.

In embodiments, a bodily fluid sample prepared in a device, system, ormethod as provided herein may reach a stated concentration of ananticoagulant (e.g. EDTA or heparin) within no more than 5, 10, 15, 20,25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 180, or210 seconds after the bodily fluid sample is initially released from asubject's body. In embodiments, a bodily fluid sample prepared in adevice, system, or method as provided herein may reach a statedconcentration of an anticoagulant (e.g. EDTA or heparin) within no morethan 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130,140, 150, 180, or 210 seconds after the skin of a subject's body ispierced (e.g. with a lancet or needle) to release the bodily fluidsample.

In embodiments, provided herein is a method comprising: receiving, in achannel, a bodily fluid sample provided by a subject; mixing the bodilyfluid sample with an anticoagulant to generate a mixed bodily fluidsample; and collecting, in a vessel in fluid communication with thechannel, the mixed bodily fluid sample, wherein the anticoagulantcomprises heparin, and wherein the mixed bodily fluid sample comprises abulk concentration of heparin no less than about 20 units per milliliterand no greater than about 150 units per milliliter. In embodiments, themixed bodily fluid sample reaches the bulk concentration of heparin at atime less than 90 seconds after the bodily fluid sample was initiallyreceived in the channel. In embodiments, mixing the bodily fluid samplewith the anticoagulant comprises mixing the bodily fluid sample with theanticoagulant with a shear rate no greater than about 1,000 reciprocalseconds.

Optionally, a method is provided comprising at least one technicalfeature from any of the disclosed embodiments.

Optionally, a method is provided comprising at least any two technicalfeatures from any of the disclosed embodiments, even if originallydescribed in separate embodiments.

Optionally, a device is provided comprising at least one technicalfeature from any of the disclosed embodiments.

Optionally, a device is provided comprising at least any two technicalfeatures from any of the disclosed embodiments, even if originallydescribed in separate embodiments.

Optionally, a system is provided comprising at least one technicalfeature from any of the disclosed embodiments.

Optionally, a system is provided comprising at least any two technicalfeatures from any of the disclosed embodiments, even if originallydescribed in separate embodiments.

This Summary is provided to introduce a selection of concepts in asimplified form that are further described below in the DetailedDescription. This Summary is not intended to identify key features oressential features of the claimed subject matter, nor is it intended tobe used to limit the scope of the claimed subject matter.

INCORPORATION BY REFERENCE

All publications, patents, and patent applications mentioned in thisspecification are herein incorporated by reference to the same extent asif each individual publication, patent, or patent application wasspecifically and individually indicated to be incorporated by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-1B show perspective views of a sample collection deviceaccording to one embodiment as described herein.

FIGS. 2A-2C show perspective views of a sample collection device withouta cap according to one embodiment as described herein.

FIGS. 3A-3B show side and cross-sectional views of a sample collectiondevice according to one embodiment as described herein.

FIGS. 4A-4B show side and cross-sectional views of a sample collectiondevice according to one embodiment as described herein.

FIGS. 5A-5B show perspective views of a sample collection deviceaccording to another embodiment as described herein.

FIGS. 6A-6B show side views of a sample collection device according toone embodiment as described herein.

FIGS. 7A-8B show side and cross-sectional views of a sample collectiondevice according to one embodiment as described herein.

FIGS. 9A-9C show side cross-sectional views of a sample collectiondevice at various stages of use according to one embodiment as describedherein.

FIGS. 10A-10B show perspective views of a sample collection deviceaccording to one embodiment as described herein.

FIGS. 11A-11Z show views of various examples of sample collectiondevices according embodiment as described herein.

FIG. 12 shows a schematic of a tip portion of a sleeve and associatedbalance of forces associated with one embodiment as described herein.

FIGS. 13A-13D show views of various collection devices with an upwardfacing collection location according to embodiments as described herein

FIGS. 14-15 show various views of a collection device with a singlecollection location according to one embodiment as described herein.

FIGS. 16-17 show perspective and end views of a sample collection deviceusing vessels having identifiers according to one embodiment asdescribed herein.

FIGS. 18A-18G show various views of sample vessels according toembodiments as described herein.

FIGS. 19A-19C show view of various embodiments of a front end of asample collection device.

FIGS. 20A-21 show various embodiments of sample collection device withan integrated tissue penetrating member.

FIG. 22 shows a perspective view of a collection device for use with ablood vessel or other tissue penetrator and sample collector accordingto an embodiment described herein.

FIG. 23-28 show various view of collection devices for use with varioussample collectors according to embodiments described herein.

FIGS. 29A-29C show schematics of various embodiments as describedherein.

FIGS. 30-31 show schematic of methods according to embodiments describedherein.

FIG. 32 shows a schematic view of one embodiment of system describedherein.

FIGS. 33 to 37 show yet another embodiment of a collection devicedescribed herein

FIGS. 38A-39 show various views of a thermally controlled transportcontainer transport device according to at least one embodimentdescribed herein.

FIGS. 40A-40C show schematics of various embodiments described herein.

FIG. 41 shows a perspective view of one portion of a transport containerhaving a plurality of sample vessels therein according to at least oneembodiment described herein.

FIG. 42 is an exploded perspective view of one portion of a transportcontainer having a plurality of sample vessels therein according to atleast one embodiment described herein.

FIG. 43 shows a perspective view of a transport container according toyet another embodiment described herein.

FIG. 44 shows a schematic of a sample collection and transport processaccording to one embodiment described herein.

FIG. 45 shows a schematic of a sample collection and transport processaccording to yet another embodiment described herein.

FIG. 46 shows a sample collection device according to one embodimentdescribed herein.

FIG. 47 shows a schematic view of one system for unloading samplevessels from a transport container according to one embodiment describedherein.

FIG. 48 is a graph showing the stability of an analyte in a sample in avessel provided herein.

FIGS. 49 to 51 show one non-limiting example of tests according to atleast one embodiment described herein.

FIGS. 52 to 55C show various views of devices and systems according toembodiments herein.

FIGS. 56A to 59B show various views of sample transport devicesaccording to at least some embodiments herein.

DETAILED DESCRIPTION

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and explanatory onlyand are not restrictive of the invention, as claimed. It may be notedthat, as used in the specification and the appended claims, the singularforms “a”, “an” and “the” include plural referents unless the contextclearly dictates otherwise. Thus, for example, reference to “a material”may include mixtures of materials, reference to “a compound” may includemultiple compounds, and the like. References cited herein are herebyincorporated by reference in their entirety, except to the extent thatthey conflict with teachings explicitly set forth in this specification.

In this specification and in the claims which follow, reference will bemade to a number of terms which shall be defined to have the followingmeanings:

“Optional” or “optionally” means that the subsequently describedcircumstance may or may not occur, so that the description includesinstances where the circumstance occurs and instances where it does not.For example, if a device optionally contains a feature for a samplecollection unit, this means that the sample collection unit may or maynot be present, and, thus, the description includes both structureswherein a device possesses the sample collection unit and structureswherein sample collection unit is not present.

As used herein, the terms “substantial” means more than a minimal orinsignificant amount; and “substantially” means more than a minimally orinsignificantly. Thus, for example, the phrase “substantiallydifferent”, as used herein, denotes a sufficiently high degree ofdifference between two numeric values such that one of skill in the artwould consider the difference between the two values to be ofstatistical significance within the context of the characteristicmeasured by said values. Thus, the difference between two values thatare substantially different from each other is typically greater thanabout 10%, and may be greater than about 20%, preferably greater thanabout 30%, preferably greater than about 40%, preferably greater thanabout 50% as a function of the reference value or comparator value.

As used herein, a “sample” may be but is not limited to a blood sample,or a portion of a blood sample, may be of any suitable size or volume,and is preferably of small size or volume. In some embodiments of theassays and methods disclosed herein, measurements may be made using asmall volume blood sample, or no more than a small volume portion of ablood sample, where a small volume comprises no more than about 5 mL; orcomprises no more than about 3 mL; or comprises no more than about 2 mL;or comprises no more than about 1 mL; or comprises no more than about500 μL; or comprises no more than about 250 μL; or comprises no morethan about 100 μL; or comprises no more than about 75 μL; or comprisesno more than about 50 μL; or comprises no more than about 35 μL; orcomprises no more than about 25 μL; or comprises no more than about 20μL; or comprises no more than about 15 μL; or comprises no more thanabout 10 μL; or comprises no more than about 8 μL; or comprises no morethan about 6 μL; or comprises no more than about 5 μL; or comprises nomore than about 4 μL; or comprises no more than about 3 μL; or comprisesno more than about 2 μL; or comprises no more than about 1 μL; orcomprises no more than about 0.8 μL; or comprises no more than about 0.5μL; or comprises no more than about 0.3 μL; or comprises no more thanabout 0.2 μL; or comprises no more than about 0.1 μL; or comprises nomore than about 0.05 μL; or comprises no more than about 0.01 μL.

As used herein, the term “point of service location” may includelocations where a subject may receive a service (e.g. testing,monitoring, treatment, diagnosis, guidance, sample collection, IDverification, medical services, non-medical services, etc.), and mayinclude, without limitation, a subject's home, a subject's business, thelocation of a healthcare provider (e.g., doctor), hospitals, emergencyrooms, operating rooms, clinics, health care professionals' offices,laboratories, retailers [e.g. pharmacies (e.g., retail pharmacy,clinical pharmacy, hospital pharmacy), drugstores, supermarkets,grocers, etc.], transportation vehicles (e.g. car, boat, truck, bus,airplane, motorcycle, ambulance, mobile unit, fire engine/truck,emergency vehicle, law enforcement vehicle, police car, or other vehicleconfigured to transport a subject from one point to another, etc.),traveling medical care units, mobile units, schools, day-care centers,security screening locations, combat locations, health assisted livingresidences, government offices, office buildings, tents, bodily fluidsample acquisition sites (e.g. blood collection centers), sites at ornear an entrance to a location that a subject may wish to access, siteson or near a device that a subject may wish to access (e.g., thelocation of a computer if the subject wishes to access the computer), alocation where a sample processing device receives a sample, or anyother point of service location described elsewhere herein.

As used herein, a “bodily fluid” may be any fluid obtained or obtainablefrom a subject. A bodily fluid may be, for example, blood, urine,saliva, tears, sweat, a bodily secretion, a bodily excretion, or anyother fluid originating in or obtained from a subject. In particular,bodily fluids include, without limitation, blood, serum, plasma, bonemarrow, saliva, urine, gastric fluid, spinal fluid, tears, stool, mucus,sweat, earwax, oil, glandular secretions, cerebral spinal fluid, semen,vaginal fluid, interstitial fluids derived from tumorous tissue, ocularfluids, placental fluid, amniotic fluid, cord blood, lymphatic fluids,cavity fluids, sputum, pus, meconium, breast milk and/or othersecretions or excretions.

As used herein, “a bodily fluid sample collector” or any othercollection mechanism can be disposable. For example, a bodily fluidcollector can be used once and disposed. A bodily fluid collector canhave one or more disposable components. Alternatively, a bodily fluidcollector can be reusable. The bodily fluid collector can be reused anynumber of times. In some instances, the bodily fluid collector caninclude both reusable and disposable components.

As used herein, “a sample collection unit” and/or any other portion ofthe device may be capable of receiving a single type of sample, ormultiple types of samples. For example, the sample collection unit maybe capable of receiving two different types of bodily fluids (e.g.,blood, tears). In another example, the sample collection unit may becapable of receiving two different types of biological samples (e.g.,urine sample, stool sample). Multiple types of samples may or may not befluids, solids, and/or semi-solids. For example, the sample collectionunit may be capable of accepting one or more of, two or more of, orthree or more of a bodily fluid, secretion and/or tissue sample.

As used herein, “non-wicked, non-matrixed form” means that a liquid orsuspension is not absorbed by or pulled into a webbing, mesh, fiber pad,absorbent material, absorbent structure, percolating network of fibers,or the like which alters the form of the liquid or suspension or trapscomponents of the sample therein to an extent that the integrity ofsample in liquid form is changed and the sample cannot be extracted inliquid form while still maintaining sample integrity for sampleanalysis.

The term “sample handling system,” as used herein, refers to a device orsystem configured to aid in sample imaging, detecting, positioning,repositioning, retention, uptake and deposition. In an example, a robotwith pipetting capability is a sample handling system. In anotherexample, a pipette which may or may not have (other) roboticcapabilities is a sample handing system. A sample handled by a samplehandling system may or may not include fluid. A sampling handling systemmay be capable of transporting a bodily fluid, secretion, or tissue. Asampling handling system may be able to transport one or more substancewithin the device that need not be a sample. For example, the samplehandling system may be able to transport a powder that may react withone or more sample. In some situations, a sample handling system is afluid handling system. The fluid handling system may comprise pumps andvalves of various types or pipettes, which, may comprise but not belimited to a positive displacement pipette, air displacement pipette andsuction-type pipette. The sample handling system may transport a sampleor other substance with aid of a robot as described elsewhere herein.

The term “health care provider,” as used herein, refers to a doctor orother health care professional providing medical treatment and/ormedical advice to a subject. A health care professional may include aperson or entity that is associated with the health care system.Examples of health care professionals may include physicians (includinggeneral practitioners and specialists), surgeons, dentists,audiologists, speech pathologists, physician assistants, nurses,midwives, pharmaconomists/pharmacists, dietitians, therapists,psychologists, chiropractors, clinical officers, physical therapists,phlebotomists, occupational therapists, optometrists, emergency medicaltechnicians, paramedics, medical laboratory technicians, medicalprosthetic technicians, radiographers, social workers, and a widevariety of other human resources trained to provide some type of healthcare service. A health care professional may or may not be certified towrite prescriptions. A health care professional may work in or beaffiliated with hospitals, health care locations and other servicedelivery points, or also in academic training, research andadministration. Some health care professionals may provide care andtreatment services for patients in private or public domiciles,community centers or places of gathering or mobile units. Communityhealth workers may work outside of formal health care institutions.Managers of health care services, medical records and health informationtechnicians and other support workers may also be medical careprofessionals or affiliated with a health care provider. A health careprofessional may be an individual or an institution that providespreventive, curative, promotional or rehabilitative health care servicesto individuals, families, or communities.

In some embodiments, the health care professional may already befamiliar with a subject or have communicated with the subject. Thesubject may be a patient of the health care professional. In someinstances, the health care professional may have prescribed the subjectto undergo a clinical test. The health care professional may haveinstructed or suggested to the subject to undergo a clinical testconducted at the point of service location or by a laboratory. In oneexample, the health care professional may be the subject's primary carephysician. The health care professional may be any type of physician forthe subject (including general practitioners, referred practitioners orthe patient's own physician optionally selected or connected throughtelemedicine services, and/or specialists). The health care professionalmay be a medical care professional.

The term “rack,” as used herein, refers to a frame or enclosure formounting multiple modules. The rack is configured to permit a module tobe fastened to or engaged with the rack. In some situations, variousdimensions of the rack are standardized. In an example, a spacingbetween modules is standardized as multiples of at least about 0.5inches, or 1 inch, or 2 inches, or 3 inches, or 4 inches, or 5 inches,or 6 inches, or 7 inches, or 8 inches, or 9 inches, or 10 inches, or 11inches, or 12 inches.

The term “cells,” as used in the context of biological samples,encompasses samples that are generally of similar sizes to individualcells, including but not limited to vesicles (such as liposomes), cells,virions, and substances bound to small particles such as beads,nanoparticles, or microspheres. Characteristics include, but are notlimited to, size; shape; temporal and dynamic changes such as cellmovement or multiplication; granularity; whether the cell membrane isintact; internal cell contents, including but not limited to, proteincontent, protein modifications, nucleic acid content, nucleic acidmodifications, organelle content, nucleus structure, nucleus content,internal cell structure, contents of internal vesicles, ionconcentrations, and presence of other small molecules such as steroidsor drugs; and cell surface (both cellular membrane and cell wall)markers including proteins, lipids, carbohydrates, and modificationsthereof.

As used herein, “sample” refers to an entire original sample or anyportion thereof, unless the context clearly dictates otherwise.

The invention provides systems and methods for multi-purpose analysis ofa sample or health parameter. The sample may be collected and one ormore sample preparation step, assay step, and/or detection step mayoccur on a device. Various aspects of the invention described herein maybe applied to any of the particular applications, systems, and devicesset forth below. The invention may be applied as a stand alone system ormethod, or as part of an integrated system, such as in a systeminvolving point of service health care. In some embodiments, the systemmay include externally oriented imaging technologies, such as ultrasoundor MRI or be integrated with external peripherals for integrated imagingand other health tests or services. It shall be understood thatdifferent aspects of the invention can be appreciated and practiceindividually, collectively, or in combination with each other.

Referring now to FIGS. 1A-1B, one embodiment of a sample collectiondevice 100 will now be described. In this non-limiting example, thesample collection device 100 may include a collection device body 120,support 130, and base 140. In some instances, a cap 110 may beoptionally provided. In one embodiment, the cap may be used to protectthe opening, keeping it clean, and for covering up the bloody tip aftercollection. Optionally or alternatively, the cap may also be used tolimit flow rate during transfer of sample fluid into the sample vesselsby controlling the amount of venting provided to the capillaries. Someembodiments may include vents pathways (permanently open or operablyclosable) in the cap while others do not. Optionally, the collectiondevice body 120 can include a first portion of the device 100 having oneor more collection pathways such as but not limited to collectionchannels 122 a, 122 b therein, which may be capable of receiving sampleB. FIG. 1A shows that sample B only partially filling the channels 122a, 122 b, but it should be understood that, although partial fills arenot excluded in some alternative embodiments, in most embodiments, thechannels will be fully filled with sample B when the fill process iscompleted. In this embodiment, the base 140 may have one or more fillindicators 142 a, 142 b, such as but not limited to optical indicators,that may provide an indication of whether sample has reached one or morevessel housed in the base. It should be understood that although thisindication may be by way of a visual indication, other indicationmethods such as audio, vibratory, or other indication methods may beused in place of or in combination with the indication method. Theindicators may be on at least one of the vessels. There may bevariations and alternatives to the embodiments described herein and thatno single embodiment should be construed to encompass the entireinvention.

Although not shown for ease of illustration, the support 130 may alsoinclude one or more fill indicators showing whether a desired fill levelhas been reached in the channels 122 a and 122 b. This may be in placeof or in addition to fill indicators 142 a, 142 b. Of course, the one ormore pathway fill indicators can be positioned on a different part andis not limited to being on support 130. It should be understood thatalthough this indication of fill level in one or more of the channels122 a and 122 b may be by way of a visual indication, other indicationmethods such as audio, vibratory, or other indication methods may beused in place of or in combination with the indication method. Theindicator may be on at least one of the collection pathways. Optionally,indicators are on all of the collection pathways.

In the present embodiment, the support 130 can be used to join the body120 and the base 140 to form an integrated device. It should beunderstood that although the device body 120, support 130, and base 140are recited as separate parts, one or more of those parts may beintegrally formed to simplify manufacturing and such integration is notexcluded herein.

In some embodiments herein, a cap 110 may be optionally provided. In onenon-limiting example, the cap may be fitted over a portion of thecollection device body 120. The cap 110 may be detachable from thecollection device body 120. In some instances, the cap 110 may becompletely separable from the collection device body 120, or may retaina portion that is connected to the collection device body, such as butnot limited to being hinged or otherwise linked to the collectiondevice. The cap 110 may cover a portion of the collection device body120 containing exposed ends of one or more channels therein. The cap 110may prevent material, such as air, fluid, or particulates, from enteringthe channels within the device body, when the cap is in place.Optionally, the cap 110 may attach to the collection body 120 using anytechnique known or later developed in the art. For instance, the cap maybe snap fit, twist on, friction-fit, clamp on, have magnetic portions,tie in, utilize elastic portions, and/or may removably connect to thecollection device body. The cap may form a fluid-tight seal with thecollection device body. The cap may be formed from an opaque,transparent, or translucent material.

In one embodiment, a collection device body 120 of a sample collectiondevice may contain at least a portion of one or more collection pathwayssuch as but not limited to channels 122 a, 122 b therein. It should beunderstood that collection pathways that are not channels are notexcluded. The collection device body may be connected to a support 130that may contain a portion of one or more channels therein. Thecollection device body may be permanently affixed to the support or maybe removable with respect to the support. In some instances, thecollection device body and the support may be formed of a singleintegral piece. Alternatively, the collection device body and supportmay be formed from separate pieces. During the operation of the devicethe collection device and support do not move relative to one another.

Optionally, the collection device body 120 may be formed in whole or inpart from an optically transmissive material. For example, thecollection device body may be formed from a transparent or translucentmaterial. Optionally, only select portion of the body are transparent ortranslucent to visualize the fluid collection channel(s). Optionally,the body comprises an opaque material but an opening and/or a window canbe formed in the body to show fill levels therein. The collection devicebody may enable a user to view the channels 122 a, 122 b within and/orpassing through the device body. The channels may be formed of atransparent or translucent material that may permit a user to seewhether sample B has traveled through the channels. The channels mayhave substantially the same length. In some instances a support 130 maybe formed of an opaque material, a transparent material, or atranslucent material. The support may or may not have the same opticalcharacteristics of the collection device body. The support may be formedfrom a different material as the collection device body, or from thesame material as the collection device body.

The collection device body 120 may have any shape or size. In someexamples, the collection device body may have a circular, elliptical,triangular, quadrilateral (e.g., square, rectangular, trapezoidal),pentagonal, hexagonal, octagonal, or any other cross-sectional shape.The cross-sectional shape may remain the same or may vary along thelength of the collection device body. In some instances, the collectiondevice body may have a cross-sectional area of less than or equal toabout 10 cm², 7 cm², 5 cm², 4 cm², 3 cm², 2.5 cm², 2 cm², 1.5 cm², 1cm², 0.8 cm², 0.5 cm², 0.3 cm², or 0.1 cm². The cross-sectional area mayvary or may remain the same along the length of the collection devicebody 120. The collection device body may have a length of less than orequal to about 20 cm, 15 cm, 12 cm, 10 cm, 9 cm, 8 cm, 7 cm, 6 cm, 5 cm,4 cm, 3 cm, 2 cm, 1 cm, 0.5 cm, or 0.1 cm. The collection device body120 may have a greater or lesser length than the cap, support or base,or an equal length to the cap, support, or base. There may be variationsand alternatives to the embodiments described herein and that no singleembodiment should be construed to encompass the entire invention.

In one embodiment, the collection pathways such as but not limited tochannels 122 a, 122 b may also have a selected cross-sectional shape.Some embodiments of the channels may have the same cross-sectional shapealong the entire length of the channel. Optionally, the cross-sectionalshape may remain the same or may vary along the length. For example,some embodiments may have one shape at one location and a differentshape at one or more different locations along the length of thechannel. Some embodiments may have one channel with one cross-sectionalshape and at least one other channel of a different cross-sectionalshape. By way of non-limiting example, some may have a circular,elliptical, triangular, quadrilateral (e.g., square, rectangular,trapezoidal), pentagonal, hexagonal, octagonal, or any othercross-sectional shape. The cross-sectional shape may be the same for thebody, support, and base, or may vary. Some embodiments may select ashape to maximize volume of liquid that can be held in the channels fora specific channel width and/or height. Some may have one of thechannels 122 a, 122 b with one cross-sectional shape while anotherchannel has a different cross-sectional shape. In one embodiment, thecross-sectional shape of the channel can help maximize volume therein,but optionally, it can also optimize the capillary pulling forces on theblood. This will allow for maximized rate of filling. It should beunderstood that in some embodiments, the cross-sectional shape of thechannel can directly affect the capillary forces. By way of non-limitingexample, a volume of sample can be contained in a shallow but widechannel, or a rounded channel, both containing the same volume, but onemight be desirable over the other for filling speed, less possibility ofair entrapment, or factors related the performance of the channel.

Although the channels may have any shape or size, some embodiments areconfigured such that the channel exhibits a capillary action when incontact with sample fluid. In some instances, the channel may have across-sectional area of less than or equal to about 10 mm², 7 mm², 5mm², 4 mm², 3 mm², 2.5 mm², 2 mm², 1.5 mm², 1 mm², 0.8 mm², 0.5 mm², 0.3mm², or 0.1 mm². The cross-sectional size may remain the same or mayvary along the length. Some embodiments may tailor for greater forcealong a certain length and then less in a different length. Thecross-sectional shape may remain the same or may vary along the length.Some channels are straight in configuration. Some embodiments may havecurved or other shaped path shapes alone or in combination with straightportions. Some may have different orientations within the device body120. For example, when the device is held substantially horizontally,one or more channels may slope downward, slope upward, or not slope atall as it carries fluid away from the initial collection point on thedevice.

The channels 122 a, 122 b may be supported by the device body 120 and/orthe support 130. In some instances, the entire length of the channelsmay be encompassed within the combination of the device body and thesupport. In some instances, a portion of the channels may be within thedevice body and a portion of the channels may be within the support. Theposition of the channels may be affixed by the device body and/or thesupport. In some embodiments, the channels may be defined as lumensinside a hollow needle. In some embodiments, the channels are onlydefined on three sides, with at least one side that is open. Optionally,a cover layer separate from the body may define the side that wouldotherwise be open. Some embodiments may define different sides of thechannel with different materials. These materials can all be provided bythe body or they may be provided by different pieces of the collectiondevice. Some embodiments may have the channels all in the same plane.Optionally, some may have a shape that takes at least a portion of thechannel to a different plane and/or orientation. Optionally, somechannels may be entirely in a different plane and/or orientation.

In some instances, a plurality of channels may be provided. In someembodiments, one channel splits into two or more channels. Optionally,some channels split into an even larger number of channels. Somechannels may include a control mechanism such as but not limited to avalve for directing flow in the channel(s). At least a portion of thechannels may be substantially parallel to one another. Alternatively, noportion of the channels need be parallel to one another. In someinstances, at least a portion of the channels are not parallel to oneanother. Optionally, the channels may be slightly bent. Optionally,channels may have one cross-sectional area at one location and a smallercross-sectional area at a different location along the channel.Optionally, channels may have one cross-sectional area at one locationand a larger cross-sectional area at a different location along thechannel. For some embodiments of the Y design, it may be desirable thatthe channels would have vents placed appropriately to define the samplefor each vial such that there would not be sample pulled or crosscontamination from other channels. By way of non-limiting example, oneembodiment with vents is shown in FIG. 11I.

A base 140 may be provided within the sample collection device. The basemay be connected to the support 130. In some instances, a portion of thebase may insertable within the support and/or a portion of the supportmay be insertable within the base. The base may be capable of movingrelative to the support. In some instances, a sample collection devicemay have a longitudinal axis extending along the length of the samplecollection device. The base and/or support may move relative to oneanother in the direction of the longitudinal axis. The base and/orsupport may be capable of moving a limited distance relative to oneanother. Alternatively, the base may be fixed relative to the support.The base may be provided at an end of the sample collection deviceopposite an end of the sample collection device comprising a cap 110.Optionally, some embodiments may include an integrated base/vessel partso that there are no longer separate vessels that are assembled into thebase pieces. There may be variations and alternatives to the embodimentsdescribed herein and that no single embodiment should be construed toencompass the entire invention.

A base 140 may house one or more vessel therein. The vessels may be influidic communication with the channels and/or may be brought intofluidic communication with the channels. An end of a channel may bewithin the vessel or may be brought within the vessel. A base may haveone or more optical indicator 142 a, 142 b that may provide a visualindication of whether sample has reached one or more vessel housed inthe base. In some embodiments, the optical indicators may be opticalwindows that may enable a user to see into the base. The optical windowmay be formed from a transparent and/or translucent material.Alternatively, the optical window may be an opening without any materialtherein. The optical window may enable a user to directly view a vesselwithin the base. The vessel within the base may be formed from atransparent and/or translucent material that may enable a user to see ifa sample has reached the vessel of the base. For example, if blood istransported along the channel to the vessels, the vessels may visuallyindicate the presence of blood therein. In other embodiments, theoptical indicators may include other features that may indicate thevessel has been filled. For example, one or more sensors may be providedwithin the base or vessel that may determine whether a sufficient amountof sample has been provided within the vessel. The one or more sensorsmay provide a signal to an optical indicator on the base that mayindicator whether the sample has been provided to the vessel and/or theamount of sample that has been provided to the vessel. For example, theoptical indicator may include a display, such as but not limited to anLCD display, light display (e.g., LED display), plasma screen displaythat may provide an indication that the vessels have been sufficientlyfilled. In alternative embodiments, an optical indicator need not beprovided, but alternative indicators may be provided, such as but notlimited to an audio indicator or temperature controlled indicator can beused to indicate when the vessels have been filed.

FIGS. 2A-2C provide views of a sample collection device 200 without acap 110. The sample collection device 200 may include a body 220,support 230, and base 240. The body may be connected to the support. Inthe present embodiment, the base 240 may be connected to the support atan end opposing the end connected to the body. The body may supportand/or contain at least a portion of one, two, or more channels 222 a,222 b. The channels may be capable of receiving a sample 224 a, 224 bfrom a sample receiving end 226 of the device.

The body 220 may have a hollow portion 225 therein. Alternatively, thebody may be formed from a solid piece. The channels 222 a, 222 b may beintegrally formed into the body. For example, they may be passagewaysthat pass through a solid portion of the body. The passageways may havebeen drilled through, or formed using lithographic techniques.Alternatively, the channels may be separate structures that may besupported by the body. For example, the channels may be formed of one ormore tube that may be supported by the body. In some instances, thechannels may be held in place at certain solid portions of the body andmay pass through one or more hollow portion of the body. Optionally, thebody 220 may be formed from two pieces joined together to define thechannels 222 a and 222 b therein.

The channels 222 a, 222 b may include one or more features orcharacteristics mentioned elsewhere herein. At least a portion of thechannels may be substantially parallel to one another. Alternatively,the channels may be at angles relative to one another. In someembodiments, the channels may have a first end that may be at a samplereceiving end 226 of the sample collection device. The first end of achannel may be an open end capable of receiving a sample. In someembodiments, the ends of each of the channels may be provided at thesample receiving end of the sample collection device. One, two, or morechannels may have a first end at the sample receiving end of the samplecollection device. Separate channels can be used to minimize the risk ofcross contamination of blood between one channel and another channel.Optionally, the channels may have an inverted Y configuration with thechannels starting with a common channel and the splitting into two ormore separate channels. This Y configuration may be useful in situationwhere contamination is not an issue. Optionally, an alternative methodto a Y configuration would be a straight channel and have the samplecollection vessels move to sequentially to engage the same needle from astraight channel.

In some instances, a plurality of channels may be provided. The ends ofthe channels at the sample receiving end may be in close proximity toone another. The ends of the channels at the sample receiving end may beadjacent to one another. The ends of the channels at the samplereceiving end may be contacting one another, or may be within about 0.5mm, 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 12 mm,15 mm, or 20 mm of one another edge to edge, or center to center. Thechannels may diverge from one another from the sample receiving end. Forexample, the other ends of the channels opposing the ends of thechannels at the sample receiving ends may be further apart from oneanother. They may be greater than or equal to about 3 mm, 4 mm, 5 mm, 6mm, 7 mm, 8 mm, 9 mm, 10 mm, 12 mm, 15 mm, 20 mm, 25 mm, or 30 mm apartfrom one another edge to edge or center to center.

In some embodiments, the body 220 may have an elongated shape. The bodymay have one or more tapered portion 228 at or near the sample receivingend 226. The sides of the body may converge at the sample receiving end.The tapered portion and/or sample receiving end may be curved.Alternatively, edges may be provided. A surface of the tapered portionmay be provided at any angle relative to the longitudinal axis of thedevice. For example, the tapered portion may be about 5 degrees, 10degrees, 15 degrees, 30 degrees, 45 degrees, 60 degrees, or 75 degreesrelative to the longitudinal axis.

The sample receiving end 226 of the device may be contacted to a sample.The sample may be provided directly from the subject. The samplereceiving end may contact the subject or a sample that is contacting orbeing exuded from the subject. For example, the sample receiving end maycontact a drop of blood on a subject's finger. The blood may enter thechannels. The blood may be transported through the channels viacapillary action, pressure differential, gravity, or any other motiveforce. The blood may travel through the channels from a sample receivingend to a sample delivery end. The sample delivery end may be in fluidcommunication or may be brought into fluid communication with one ormore vessels housed within a base of the device. The sample may passfrom the channels to the vessels. The sample may be driven into thevessels via pressure differential, capillary action, gravity, friction,and/or any other motive force. Optionally, the sample might also beblood introduced with a pipette, syringe, etc. . . . It should beunderstood that although FIG. 2B shows that sample B only partiallyfilling the channels 222 a, 222 b, but in most embodiments, the channelswill be fully filled with sample B when the fill process is completed.

FIGS. 3A-3B show an example of a sample collection device 300 prior tobringing the channels 322 a, 322 b into fluid communication with one ormore vessels 346 a, 346 b housed within a base 340 of the device. Thesample collection device may include a cap 310, body 320, support 330,and base 340. The body and/or support may support and/or encompass atleast a portion of one, two, or more channels. The base may supportand/or encompass one, two, or more vessels.

In one embodiment, a body 320 and/or support 330 may support one or morechannels 322 a, 322 b in the sample collection device. In one example,two channels are provided, although descriptions relating to atwo-channel embodiment may apply to any number of channels including butnot limited to 1, 3, 4, 5, 6, or more channels. Each of the channels mayhave a first end 323 a, 323 b that may be provided at a sample receivingend 326 of the device. The first ends of the respective channels may beopen. The channels may be open to ambient air. When the first ends ofthe channels contact a fluid, such as blood, the fluid may be drawn intothe channels. Blood may be drawn in via capillary action, or any otherof the techniques described elsewhere herein. The blood may travel alongthe length of the channels to the respective second ends 325 a, 325 b ofthe channels. The channels may be fluidically segregated from oneanother. For example, a fluid may enter a first channel 322 a via afirst end 323 a, pass through the length of the channel, and exit thefirst channel at the second end 325 a. Similarly, fluid may enter asecond channel 322 b via a first end 323 b, pass through the length ofthe channel, and exit the second channel at the second end 325 b. Thefirst and second channels may be fluidically segregated so that fluidfrom the first channel does not pass into the second channel and viceversa. In some embodiments, the fluid may pass to the second ends of thechannels without exiting initially.

The channels 322 a, 322 b may have a diverging configuration. Forexample, the first ends 323 a, 323 b of the channels may be closertogether than the second ends 325 a, 325 b of the channels. More spacemay be provided between the second ends of the channels than between thefirst ends of the channels. The first ends of the channels may or maynot be in contact with one another. The first ends of the channels maybe adjacent to one another.

A base 340 may be connected to a support 330 of the sample collectiondevice. The base 340 may or may not directly contact the support. Thebase may be movable relative to the support during use of the device. Insome embodiments, the base may slide in a longitudinal directionrelative to the support. In some instances, the base may slide in alongitudinal direction relative to the support without rotating. In someinstances, the base may slide co-axially with the support withoutrotating. In some instances, a base may rotate while moving relative tothe support. A portion of the base may fit within a portion of thesupport, or vice versa. For example, a portion of the base may beinsertable into a portion of the support and/or a portion of the supportmay be insertable into the base. One or more stop feature may beprovided in the base and/or the frame to provide a controlled degree ofmovement between the base and the support. The stop feature may includea shelf, protrusion or groove.

The base 340 may be capable of supporting one or more vessels 346 a, 346b. The base may have a housing that may at least partially surround theone or more vessels. In some instances, the vessels may be completelysurrounded when the base is engaged with a support 330. The base mayhave one or more indentation, protrusion, groove, or shaped feature toaccept the vessels. The base may be formed with a shape that iscomplementary to the shape of the vessels. The vessels may be maintainedin an upright position relative to the base.

The same number of vessels may be provided as the number of channels.For example, if N channels are provided, then N vessels may be provided,wherein N is a positive whole number (e.g., 1, 2, 3, 4, 5, 6, 7, 8, ormore). Each channel may correspond to a respective vessel. In oneexample, a sample collection device may have a first channel and asecond channel, as well as a respective first vessel and second vessel.A first channel 322 a may be in or may be configured to be brought intofluid communication with a first vessel 346 a, and a second channel 322b may be in or may be configured to be brought into fluid communicationwith a second vessel 346 b.

In some embodiments, each vessel may have a body 349 a, 349 b and a cap348 a, 348 b. In some instances, the vessel body may be formed from atransparent or translucent material. The vessel body may permit a sampleprovided within the vessel body to be visible when viewed from outsidethe vessel. The vessel body may have a tubular shape. In some instances,the vessel body may have a cylindrical portion. The bottom of the vesselmay be flat, tapered, rounded, or any combination thereof. The vesselsmay comprise an open end and a closed end. The open end may be a top endof the vessel, which may be at the end of the vessel closer to one ormore channel. The closed end may be a bottom end of the vessel, whichmay be at the end of the vessel further from one or more channel.Various embodiments of vessels may be described in greater detailelsewhere herein.

A base 340 may have one or more optical indicators, such as opticalwindows 342 a, 342 b. The optical windows may be positioned over thevessels 346 a, 346 b. In some instances, the optical windows may bepositioned over the vessel bodies. A single window may provide a view toa single vessel or to multiple vessels. In one example, the same numberof optical windows may be provided as vessels. Each optical window maycorrespond to a respective vessel. Both the optical window and vesselsmay be formed of an optically transmissive material that may permit auser to view whether a sample has reached the vessel from outside thesample collection device.

In some embodiments, there may be optical windows of the channels 322 aand 322 b so that a user may observe when a desired fill level has beenreached in the channels. Some embodiments where the body 320 is entirelytransparent or translucent, there may be a marker or indicator markalong the channels to note when a desired fill level has been reached.

The vessels may be sized to contain a small fluid sample. In someembodiments, the vessels may be configured to contain no more than about5 ml, 4 ml, 3 ml, 2 ml, 1.5 mL, 1 mL, 900 μL, 800 μL, 700 μL, 600 μL,500 μL, 400 μL, 300 μL, 250 μL, 200 μL, 150 μL, 100 μL, 80 μL, 50 μL, 30μL, 25 μL, 20 μL, 10 μL, 7 μL, 5 μL, 3 μL, 2 μL, 1 μL, 750 nL, 500 nL,250 nL, 200 nL, 150 nL, 100 nL, 50 nL, 10 nL, 5 nL, or 1 nL. The vesselsmay be configured to contain no more than several drops of blood, a dropof blood, or no more than a portion of a drop of blood.

The vessels may contain a cap 348 a, 348 b. The plug may be configuredto fit over an open end of the vessel. The cap may block the open end ofthe vessel. The cap may fluidically seal the vessel. The cap may form afluid-tight seal with the vessel body. For example, the cap may be gasand/or liquid impermeable. Alternatively, the cap may permit certaingases and/or liquids to pass through. In some instances, the cap may begas permeable while being liquid impermeable. The cap may be impermeableto the sample. For example, the cap may be impermeable to whole blood,serum or plasma. In some instances, a portion of the cap may fit into aportion of the vessel body. The cap may form a stopper with the vesselbody. The cap may include a lip or shelf that may hang over a portion ofthe vessel body. The lip or shelf may prevent the cap from sliding intothe vessel body. In some instances, a portion of a cap may overlie a topand/or side of the vessel body. Any description herein of vessels may beapplied in combination with the sample collection device. Optionally,some embodiments may include an additional part in the vessel assemblysuch as cap holder. In one embodiment, the purpose of the cap holder isto maintain a tight seal between the cap and vessel. In one embodiment,the cap holder engages an attachment, lip, indentation, or otherattachment location on the outside of the vessel to hold the cap inposition. Optionally, some embodiments can combine the function of boththe cap and the cap holder into one component.

One or more engagement assemblies may be provided. The engagementassembly may include a channel holder 350 and/or a force-exertingcomponent, such as a spring 352 or elastic. In one embodiment, theholder 350 may keep the adapter channel 354 affixed to the support. Aswill be described elsewhere herein, the adaptor channel 354 may beformed integrally with the collection channel or may be a discreteelement that may be a stand-alone piece, part of the collection channel,or part of the vessel. In one embodiment, the holder 350 may prevent theadapter channel 354 from sliding relative to the support. The holder 350may optionally provide a support upon which a force-exerting component,such as a spring, may rest.

In one example, the engagement assemblies may each include a spring 352which may exert a force so that the base 340 is at an extended state,when the spring is at its natural state. When the base is at itsextended state, space may be provided between the vessels 346 a, 346 band the engagement assemblies. In some instances, when the base 340 isin its extended state, the second ends of the channels may or may notcontact the caps of the vessels. The second ends of the channels 325 a,325 b may be in a position where they are not in fluid communicationwith the interiors of the vessels.

A sample collection device may have any number of engagement assemblies.For example, the same number of engagement assemblies may be provided asnumber of channels. Each channel may have an engagement assembly. Forexample, if a first channel and a second channel are provided, a firstengagement assembly may be provided for the first channel, and a secondengagement assembly may be provided for the second channel. The samenumber of engagement assemblies and vessels may be provided.

In one embodiment, the engagement assembly may house an adapter channel354 such as but not limited to an elongate member with angled, taperedor pointed end 327 a and 327 b. It should be understood that in someembodiments, the ends 327 a and 327 b are part of a needle that isformed separate from the channels 322 a and 322 b and then coupled tothe channels 322 a and 322 b. The needles may be formed of the same ordifferent material from the body defining the channels 322 a and 322 b.For example, some may use a metal to form the needles and a polymer orplastic material for the body defining channels 322 a and 322 b.Optionally, some embodiments may form the ends 327 a and 327 b on amember that is integrally formed with the channels 322 a and 322 b. Insome instances, the second end of the channel may be configured topenetrate a material, such as a cap 348 a, 348 b of the vessel. In someembodiments, a portion of the adaptor channel 354 may be insertablewithin the collection channel or a portion of the collection channel maybe insertable within the adaptor channel, or the two may be configuredto align flush. Optionally, some embodiments may integrally form theadapter channel 354 with the collection channel 322 a. It should beunderstood that FIGS. 3B (and 4B) shows that sample B only partiallyfilling the channels 122 a, 122 b, but, in most embodiments, thechannels will be fully filled with sample B when the fill process iscompleted. There may be variations and alternatives to the embodimentsdescribed herein and that no single embodiment should be construed toencompass the entire invention.

FIGS. 4A-4B show an example of a sample collection device 400 havingchannels 422 a, 422 b that are in fluid communication with the interiorof vessels 446 a, 446 b within the device. The sample collection devicemay include a cap 410, body 420, support 430, and base 440. The bodyand/or support may support and/or encompass at least a portion of one,two, or more channels. The base may support and/or encompass one, two,or more vessels.

In one embodiment, a body 420 and/or support 430 may support one or morechannels 422 a, 422 b in a sample collection device. For example, afirst channel and second channel may be provided. Each of the channelsmay have a first end 423 a, 423 b that may be provided at a samplereceiving end 426 of the device. The first ends of the respectivechannels may be open. The channels may be open to ambient air. When thefirst ends of the channels contact a fluid, such as blood, the fluid maybe drawn into the channels. The fluid may be drawn in via capillaryaction, or any other of the techniques described elsewhere herein. Thefluid may travel along the length of the channels to the respectivesecond ends 425 a, 425 b of the channels. In some embodiments, the fluidmay reach the second ends of the channels via capillary action or othertechniques described herein. In other embodiments, the fluid need notreach the second ends of the channels. The channels may be fluidicallysegregated from one another.

In some embodiments, the fluid may pass to the second ends of thechannels without exiting when the channels are not in fluidcommunication with the interiors of the vessels 446 a, 446 b. Forexample, the fluid may be drawn into the channel via capillary action,which may cause the fluid to flow to or near the end of the channelwithout causing the fluid to exit the channel.

A base 440 may be connected to a support 430 of the sample collectiondevice. The base may be movable relative to the support during use ofthe device. In some embodiments, the base may slide in a longitudinaldirection relative to the support. In one example, the base may have (i)an extended position where the channels are not in fluid communicationwith the interior of the vessels, and (ii) a compressed position wherethe channels are in fluid communication with the interior of thevessels. A sample collection device may be initially provided in anextended state, as shown in FIG. 3. After the sample has been collectedand flown through the length of the channel, a user may push the base into provide the sample collection device in its compressed state, asshown in FIG. 4. Once the base has been pushed in, the base maynaturally remain pushed in, or may spring back out to an extended state,once the pushing force is removed. In some instances, a base may bepulled out to an extended state, or may be pulled out completely toprovide access to vessels therein.

The base 440 may be capable of supporting one or more vessels 446 a, 446b. The base may have a housing that may at least partially surround theone or more vessels. In some instances, the vessels may be completelysurrounded when the base is engaged with a support 430. The base mayhave one or more indentation, protrusion, groove, or shaped feature toaccept the vessels. The base may be formed with a shape that iscomplementary to the shape of the vessels. The vessels may be maintainedin an upright position relative to the base.

The same number of vessels may be provided as the number of channels.Each channel may correspond to a respective vessel. In one example, asample collection device may have a first channel and a second channel,as well as a respective first vessel and second vessel. A first channel422 a may be in or may be configured to be brought into fluidcommunication with a first vessel 446 a, and a second channel 422 b maybe in or may be configured to be brought into fluid communication with asecond vessel 446 b. The first channel may initially not be in fluidcommunication with a first vessel and the second channel may initiallynot be in fluid communication with the second vessel. The first andsecond channels may be brought into fluid communication with theinteriors of the first and second vessels respectively when the base ispushed in relative to the support. The first and second channels may bebrought into fluid communication with the first and second vesselssimultaneously. Alternatively, they need not be brought into fluidcommunication simultaneously. The timing of the fluid communication maydepend on the height of the vessel and/or the length of the channel. Thetiming of the fluid communication may depend on the relative distancesbetween the second end of the channel and the vessel.

In some embodiments, each vessel may have a body 449 a, 449 b and a cap448 a, 448 b. The vessel body may have a tubular shape. In someinstances, the vessel body may have a cylindrical portion. The bottom ofthe vessel may be flat, tapered, rounded, or any combination thereof.The vessels may comprise an open end and a closed end. The open end maybe a top end of the vessel, which may be at the end of the vessel closerto one or more channel. The closed end may be a bottom end of thevessel, which may be at the end of the vessel further from one or morechannel.

A base 440 may have one or more optical indicators, such as opticalwindows 442 a, 442 b. The optical windows may be positioned over thevessels 446 a, 446 b. In some instances, the optical windows may bepositioned over the vessel bodies. Both the optical window and vesselsmay be formed of an optically transmissive material that may permit auser to view whether a sample has reached the vessel from outside thesample collection device. In some embodiments, the vessels mayincorporate markings on the vessels themselves to indicate fill levelrequirements.

The vessels may contain a cap 448 a, 448 b. The cap may be configured tofit over an open end of the vessel. The cap may block the open end ofthe vessel. The cap may fluidically seal the vessel. The cap may form afluid-tight seal with the vessel body. For example, the cap may beimpermeable to whole blood, serum or plasma. In some instances, aportion of the cap may fit into a portion of the vessel body. The capmay include a lip or shelf that may hang over a portion of the vesselbody. In some embodiments, the cap may have a hollow or depression. Thehollow or depression may assist with guiding a second end of the channelto a center of the cap. In some instances, when the sample collectiondevice is in an extended state, a second end of a channel 425 a, 425 bmay lie above the cap of the vessel. The second end of the channel mayor may not contact the vessel cap. In some instances, the second end ofthe channel may rest within a hollow or depression of the cap. In someinstances, the second end of the channel may partially penetrate the capwithout reaching the interior of the vessel. Optionally, someembodiments of the cap might include a crimping piece to hold vacuum.

A second end of a channel may have an angled, tapered or pointed end 427a and 427 b. It should be understood that in some embodiments, the ends427 a and 427 b are part of a needle that is formed separate from thechannels 422 a and 422 b and then coupled to the channels 422 a and 422b. The needles may be formed of the same or different material from thebody defining the channels 422 a and 422 b. For example, some may use ametal to form the needles and a polymer or plastic material for the bodydefining channels 422 a and 422 b. Optionally, some embodiments may formthe ends 427 a and 427 b on a member that is integrally formed with thechannels 422 a and 422 b. In some instances, the second end of thechannel may be configured to penetrate a material, such as a cap 448 a,448 b of the vessel. The cap may be formed of a material that mayprevent sample from passing through in the absence of a penetratingmember. The cap may be formed from a single solid piece. Alternatively,the cap may include a slit, opening, hole, thin portion, or any otherfeature that may accept a penetrating member. A slit or other openingmay be capable of retaining sample therein, when the penetrating memberis not in the slit or opening, or when the penetrating member is removedfrom the slit or opening. In some instances, the cap may be formed froma self-healing material, so that when a penetrating member is removed,the opening formed by the penetrating member closes up. The second endof the channel may be a penetrating member that may pass through the capand into the interior of the vessel. In some embodiment, it should beclear that the penetrating member may be hollow needles that allowsample to pass through, and not just needles for piercing. In someembodiments, the piercing tip can be a non-coring design such as but notlimited to a tapered cannula that pierces without coring the capmaterial.

One or more engagement assemblies may be provided. The engagementassembly may include a channel holder 450 and/or a force-exertingcomponent, such as a spring 452 or elastic. In one embodiment, theholder 450 may keep the adaptor channel 454 affixed to the support. Aswill be described elsewhere herein, the adaptor channel 454 may beformed integrally with the collection channel or may be a discreteelement that may be a stand-alone piece, part of the collection channel,or part of the vessel. In one embodiment, the holder 450 may prevent theadaptor channel 454 from sliding relative to the support. The holder 450may optionally provide a support upon which a force-exerting component,such as a spring, may rest.

In one example, the engagement assemblies may include a spring 452 whichmay exert a force so that the base is at its extended state, when thespring is at its natural state. When the base is at its extended state,space may be provided between the vessels 446 a, 446 b and theengagement assemblies. The second ends of the channels 425 a, 425 b maybe in a position where they are not in fluid communication with theinteriors of the vessels.

A sample collection device may have any number of engagement assemblies.For example, the same number of engagement assemblies may be provided asnumber of channels. Each channel may have an engagement assembly. Forexample, if a first channel and a second channel are provided, a firstengagement assembly may be provided for the first channel, and a secondengagement assembly may be provided for the second channel. In oneembodiment, the same number of engagement assemblies and vessels may beprovided.

When the base is pressed in, the spring 452 may be compressed. Thesecond ends 425 a, 425 b of the channels may penetrate the caps of thevessels. The second ends of the channels may enter the interior of thevessel. In some instances, a force may be provided to drive the fluidfrom the channels into the vessels. For example, a pressure differentialmay be generated between the first and second ends of the channels. Apositive pressure may be provided at the first end 423 a, 423 b of thechannels and/or a negative pressure may be provided at the second end ofthe channels. The positive pressure may be positive relative to thepressure at the second end of the channel, and/or ambient air. Thenegative pressure may be negative relative to the pressure at the firstend of the channel and/or ambient air. In one example, the vessels mayhave a vacuum therein. When the second end of a channel penetrates avessel, the negative pressure within the vessel may pull the sample intothe vessel. In alternative embodiments, the sample may enter the vesseldriven by capillary forces, gravity, or any other motive force. Inembodiments, the vessel does not have a vacuum therein. There may bevariations and alternatives to the embodiments described herein and thatno single embodiment should be construed to encompass the entireinvention.

In some instances, different types of motive forces may be used atdifferent stages of sample collection. Thus, one type of motive forcemay be used to draw the sample into the channel, and then a differenttype of motive force may be used to move sample from the channel intothe vessel. For example, a capillary force may draw the sample into achannel, and a pressure differential may drive the sample from thechannel into the vessel. Any combinations of motive forces may be usedto draw sample into the channel and into the vessel. In someembodiments, the motive force(s) used to draw sample into the channel isdifferent from motive force(s) used to draw sample into the vessel. Insome alternative embodiments, the motive force(s) may be the same foreach stage. In some embodiments, the motive force(s) are appliedsequentially or at defined time periods. By way of non-limiting example,motive force(s) to draw sample into the vessel is not applied until theat least one channel has reach a minimum fill level. Optionally, motiveforce(s) to draw sample into the vessel is not applied until the atleast two channels have each reach a minimum fill level for thatchannel. Optionally, motive force(s) to draw sample into the vessel isnot applied until all channels have each reach a minimum fill level forthat channel. In some embodiments, the motive force(s) are appliedsimultaneously.

Some embodiments may use a pressurized gas source coupled to the samplecollection device and configured to push collected bodily fluid from theone or more channels into their respective vessels. Optionally, some mayuse a vacuum source not associated with the vessels to pull sample fluidtowards the vessels.

Additional, some embodiments of the channel may be configured such thatthere is sufficient capillary force within the channel such that oncefilled, the force is greater than that of gravity so that sample doesnot escape from the channel based only on gravitation force. Anadditional motive force is used to break the hold of the capillaryaction of the channel(s). Optionally, as described elsewhere herein, adevice such as but not limited to a sleeve may contain the bodily fluidfrom exiting the channel at the end closest to the vessel, thusminimizing any loss until transfer to the vessel is initiated.

Optionally, other materials such as but not limited to a lyosphere,sponge, or other motive force provider may be used to provide motiveforce that draws sample into the vessel. When multiple forces are beingused, this may be a primary, secondary, or tertiary motive force to drawsample into the vessel. Optionally, some embodiments may include apush-type motive force provider such as but not limited to a plunger tomove the sample in a desired manner.

Some time may elapse after a sample has been introduced to a channel fortraveling along the length of the channel. A user may introduce a sampleto the sample collection device and may wait for the sample to travelthe length of the channel. One or more optical indicator may beprovided, which may indicate whether the sample has reached a desiredfill level, such as not limited to the end of the channel. In otherembodiments, the user may wait a predetermined amount of time beforepushing in the base. The base may be pushed in after the user hasdetermined the sample has traveled a sufficient length of the channeland/or a sufficient amount of time has passed since the sample wasintroduced. After the base is pushed in, the channels may be broughtinto fluid communication with the vessels, and sample may flow from thechannel into the vessels. An optical indicator may be provided so that auser may know when the vessels have been filled.

Once the vessels have been filled, they may be transferred to a desiredlocation, using systems and methods described elsewhere herein. In someinstances, the entire sample collection device may be transferred. Thecap may be placed on the sample collection device for transfer. In otherembodiments, the base portion and/or support portion may be removablefrom the rest of the device. In one example, the base may be removedfrom the sample collection device, and the vessels may be transferredalong with the base. Alternatively, the base may be removed from thesample collection device to provide access to the vessels, and thevessels may be removed from the device and transmitted. The removal ofthe base may involve some disassembly of the sample collection device todetach the base. This may involve using sufficient force to overcomedetents or stops built into the device to prevent accidentaldisengagement. Optionally, some other positive act such as but notlimited to disengaging a latch or other locking mechanism may beperformed by a user before detaching the base. Optionally, someembodiments may allow for removal of the vessels without removal of thebase, but allow for access to the vessels by way of openings, accessports, or open-able covers on the base.

In some embodiments, one or more of the channels and/or vessels maycomprise features described elsewhere herein, such as separationmembers, coatings, anti-coagulants, beads, or any other features. In oneexample, the sample introduced to the sample collection device may bewhole blood. Two channels and respective vessels may be provided. Inthis non-limiting example, each of the channels has a coating such asbut not limited to an anti-coagulant coating in the channel. Such ananti-coagulant coating can serve one or more of the following functions.First, the anti-coagulant can prevent whole blood from clotting insidethe channel during the sample collection process. Depending on theamount of whole blood to be collected, clotting could prematurely clogthe channel before sufficient amount of blood has been brought into thechannel. Another function is to introduce anti-coagulant into the wholeblood sample. By have the anti-coagulant in the channel, this processcan begin earlier in the collection process versus some embodimentswhich may only have it the vessels 446 a or 446 b. This earlyintroduction of anti-coagulant may also be advantageous in case thewhole blood sample will be led along a pathway that may have portionsthat are not coated with anti-coagulant, such as but not limited to, theinner surfaces of a needle connected to the channels 422 a or 422 b.Optionally, some embodiments may include surfactants that can be used tomodify the contact angle (wettability) of a surface.

In some embodiments the inner surface of the channel and/or othersurfaces along the fluid pathway such as but not limited to the sampleinlet to the interior of a sample collection vessel may be coated with asurfactant and/or an anti-coagulant solution. The surfactant provides awettable surface to the hydrophobic layers of the fluidic device andfacilitate filling of the metering channel with the liquid sample, e.g.,blood. The anti-coagulant solution helps prevent the sample, e.g.,blood, from clotting when provided to the fluidic device. Exemplarysurfactants that can be used include without limitation, Tween,TWEEN®20, Thesit®, sodium deoxycholate, Triton, Triton® X-100, Pluronicand/or other non-hemolytic detergents that provide the proper wettingcharacteristics of a surfactant. EDTA and heparin are non-limitinganti-coagulants that can be used. In one non-limiting example, theembodiment the solution comprises 2% Tween, 25 mg/mL EDTA in 50%Methanol/50% H20, which is then air dried. A methanol/water mixtureprovides a means of dissolving the EDTA and Tween, and also driesquickly from the surface of the plastic. The solution can be applied tothe channel or other surfaces along the fluid flow pathway by anytechnique that will ensure an even film over the surfaces to be coated,such as, e.g., pipetting, spraying, printing, or wicking.

It should also be understood for any of the embodiments herein that acoating in the channel may extend along the entire path of the channel.Optionally, the coating may cover a majority but not all of the channel.Optionally, some embodiments may not cover the channel in the areasnearest the entry opening to minimize the risk of cross-contamination,wherein coating material from one channel migrates into nearby channelsby way of the channels all being in contact with the target sample fluidat the same time and thus having a connecting fluid pathway.

Although embodiments herein are shown with two separate channels in thesample collection device, it should be understood that some embodimentsmay use more than two separate channels. Optionally, some embodimentsmay use less than two fully separate channels. Some embodiments may onlyuse one separate channel. Optionally, some embodiments may use aninverted Y-channel that starts initially as one channel and then splitsinto two or more channels. Any of these concepts may be adapted for usewith other embodiments described herein.

Collection Device with Self-Supporting Collection Channels

FIGS. 5A-5B provide another example of a sample collection device 500provided in accordance with an embodiment described herein. The samplecollection device may include a collection device body 520, support 530,and base 540. In some instances, a cap may be optionally provided. Thecollection device body may contain one or more collection channels 522a, 522 b defined by collection tubes, which may be capable of receivingsample. A base may have one or more optical indicator 542 a, 542 b thatmay provide a visual indication of whether sample has reached one ormore vessel housed in the base. A support may have one or more opticalindicator 532 a, 532 b that may provide a visual indication of whethersample has reached or passed through a portion of the channels.

A collection device body 520 of a sample collection device may containat least a portion of one or more tubes with channels 522 a, 522 btherein. Optionally, the device collection body 520 may also definechannels that couple to channels 522 a, 522 b defined by the tubes. Insome embodiments, a portion of the channels may extend beyond thecollection device body. The channels may extend beyond one end or twoends of the collection device body.

The collection device body 520 may be connected to a support 530. Thesupport may contain a portion of one or more channels therein. Thecollection device body may be permanently affixed to the support or maybe removable with respect to the support. In some instances, thecollection device body and the support may be formed of a singleintegral piece. Alternatively, the collection device body and supportmay be formed from separate pieces.

During the operation of the device the collection device body 520 andsupport 530 may move relative to one another. In some instances, aportion of the body 520 may be insertable within the support 530 and/ora portion of the support may be insertable within the body. The body maybe capable of moving relative to the support. In some instances, asample collection device may have a longitudinal axis extending alongthe length of the sample collection device. The body and/or support maymove relative to one another in the direction of the longitudinal axis.The body and/or support may be capable of moving a limited distancerelative to one another. The body and/or support may move co-axiallywithout rotational motion. Alternatively, rotational motion may beprovided.

The collection device body 520 may be formed from an opticallytransmissive material. For example, the collection device body may beformed from a transparent or translucent material. Alternatively, thebody may be formed from an opaque material. The support 530 may beformed from an optically opaque, translucent, or transparent material.The support may or may not have the same optical characteristics of thecollection device body. The support may be formed from a differentmaterial as the collection device body, or from the same material as thecollection device body. There may be variations and alternatives to theembodiments described herein and that no single embodiment should beconstrued to encompass the entire invention.

The collection device body, support, and/or base may have any shape orsize. In some examples, the collection device body, support, and/or basemay have a circular, elliptical, triangular, quadrilateral (e.g.,square, rectangular, trapezoidal), pentagonal, hexagonal, octagonal, orany other cross-sectional shape. The cross-sectional shape may remainthe same or may vary along the length. The cross-sectional shape may bethe same for the body, support, and base, or may vary. In someinstances, the collection device body, support, and/or base may have across-sectional area of less than or equal to about 10 cm2, 7 cm2, 5cm2, 4 cm2, 3 cm2, 2.5 cm2, 2 cm2, 1.5 cm2, 1 cm2, 0.8 cm2, 0.5 cm2, 0.3cm2, or 0.1 cm2. The cross-sectional area may vary or may remain thesame along the length. The cross-sectional size may be the same for thecollection body, support, and/or base, or may vary. The collectiondevice body, support, and/or base may have a length of less than orequal to about 20 cm, 15 cm, 12 cm, 10 cm, 9 cm, 8 cm, 7 cm, 6 cm, 5 cm,4 cm, 3 cm, 2 cm, 1 cm, 0.5 cm, or 0.1 cm. The collection device bodymay have a greater or lesser length than support or base, or an equallength to the support, or base.

The channels 522 a, 522 b may be supported by the device body 520 and/orthe support 530. In some instances, the entire length of the tubes orthe channels therein may be encompassed within the combination of thedevice body and the support. Alternatively, the channels may extendbeyond the device body and/or support as seen in FIG. 5. In someinstances, the channels may extend beyond one end of the devicebody/support combination, or beyond both ends. In some instances, aportion of the channels may be within the device body and a portion ofthe channels may be within the support. The position of the channels maybe affixed by the device body and/or the support. In some instances, thechannels may be affixed to device body and/or not move relative to thedevice body. The channels may be movable relative to the support. Insome instances, a plurality of channels may be provided. At least aportion of the channels may be substantially parallel to one another.The channels may be parallel to one another and/or a longitudinal axisextending along a length of the sample collection device. Alternatively,no portion of the channels need be parallel to one another. In someinstances, at least a portion of the channels are not parallel to oneanother. The channels may be slightly bent. Optionally, they may bestraight, but aligned to be closer to one another as they near thesample collection point. It should be understood that the tubes definingthe channels 522 a and 522 b may be made of optically transparent,transmissive, or other material sufficient to provide a detectablechange that sample has reached a desired fill level in at least onechannel. Optionally, the detectable change can be used to detect whenboth channels reach at least the desired fill level.

A base 540 may be provided within the sample collection device. The basemay be connected to the support 530. In some instances, a portion of thebase 540 may insertable within the support 530 and/or a portion of thesupport may be insertable within the base. The base may be fixedrelative to the support or may be movable relative to the support. Thebase may be provided at an end of the support opposite an end of thesupport connected to the body. The base may be formed as a separatepiece from the support. The base may be separable from the support.Alternatively, the base may be affixed to the support and/or formed asan integral piece with the support.

A base 540 may house one or more vessel therein. The vessels may be influidic communication with the channels and/or may be brought intofluidic communication with the channels. An end of a channel may bewithin the vessel or may be brought within the vessel. A base may haveone or more optical indicator 542 a, 542 b that may provide a visualindication of whether sample has reached one or more vessel housed inthe base. In some embodiments, the optical indicators may be opticalwindows that may enable a user to see into the base. The optical windowmay be formed from a transparent and/or translucent material.Alternatively, the optical window may be an opening without any materialtherein. The optical window may enable a user to directly view a vesselwithin the base. The vessel within the base may be formed from atransparent and/or translucent material that may enable a user to see ifa sample has reached the vessel of the base. For example, if blood istransported along the channel to the vessels, the vessels may show theblood therein. In other embodiments, the optical indicators may includeother features that may indicate the vessel has been filled. Forexample, one or more sensor may be provided within the base or vesselthat may determine whether a sufficient amount of sample has beenprovided within the vessel. The sensor may provide a signal to anoptical indicator on the base that may indicator whether the sample hasbeen provided to the vessel and/or the amount of sample that has beenprovided to the vessel. For example, the optical indicator may include adisplay, such as an LCD display, light display (e.g., LED display),plasma screen display that may provide an indication that the vesselshave been sufficiently filled. In alternative embodiments, an opticalindicator need not be provided, but alternative indicators may beprovided, such as but not limited to, an audio indicator, temperaturecontrolled indicator, or other device that may indicate by a detectablesignal, such as one detectable by a user, when the vessels have beenfiled.

A support 530 may have one or more optical indicator 532 a, 532 b thatmay provide a visual indication of whether sample has reached or passthrough a portion of a channel housed by the support. In someembodiments, the optical indicators may be optical windows that mayenable a user to see into the support. The optical window may be formedfrom a transparent and/or translucent material. Alternatively, theoptical window may be an opening without any material therein. Theoptical window may enable a user to directly view a portion of a channelwithin the support. The channels may be formed from a transparent and/ortranslucent material that may enable a user to see if a sample hasreached the portion of the channel underlying the optical window. Inother embodiments, the optical indicators may include other featuresthat may indicate the sample has passed through a portion of thechannel, such as sensors described elsewhere herein.

Referring now to FIGS. 6A-6B, additional views of a sample collectiondevice 500 are provided in accordance with one embodiment describedherein.

In some embodiments, a portion of the tubes containing channels 522 a,522 b may extend beyond the collection device body 520. The portion ofthe channels that extend beyond may include portions of the channelsthat are configured to receive a sample from the subject. In oneexample, the channels may have a first end 523 a, 523 b that may be asample receiving end of the channels.

The channels may optionally be defined by a rigid material.Alternatively, the channels may be defined by a flexible material or mayhave flexible components. The channels may or may not be designed tobend or curve. The channels may or may not be substantially parallel toone another. In some instances, the first ends of the channels may besome distance apart when in a relaxed state. The first ends of thechannels may remain that distance apart during operation of the device.Alternatively, the first ends of the channels may be brought closertogether. For example, the first ends of the channels may be squeezedtogether. Each open end of the channels may separately receive a sample.The sample may be received sequentially. The sample may be from the samesubject. Alternatively, the channels may be capable of receiving thesame sample simultaneously.

The channels 522 a, 522 b may include one or more features orcharacteristics mentioned elsewhere herein. At least a portion of thechannels may be substantially parallel to one another. Alternatively,the channels may be at angles relative to one another. In someembodiments, the channels may have a first end that may be at a samplereceiving end 526 of the sample collection device. The first end of achannel may be an open end capable of receiving a sample. In someembodiments, the ends of each of the channels may be provided at thesample receiving end of the sample collection device. One, two, or morechannels may have a first end at the sample receiving end of the samplecollection device.

In some embodiments, the device body 520 may be movable relative to thesupport 530. A portion of the device body may be insertable within thesupport or vice versa. In one example, the device body may have a lip527 and an interior portion 529. The lip may have a greatercross-sectional area than the interior portion. The interior portion maybe capable of being inserted into the support. The lip may act as a stopto prevent the entire body from being inserted into the support. The lipmay rest on a shoulder of the support.

FIGS. 7A-7B shows partial cutaway views of an example of a samplecollection device 700 provided in accordance with an embodimentdescribed herein. The sample collection device in an extended state,prior to bringing the channels 722 a, 722 b into fluid communicationwith one or more vessels 746 a, 746 b housed within a base 740 of thedevice. The sample collection device may include a body 720, support730, and base 740. The body and/or support may support and/or encompassat least a portion of one, two or more channels. The base may supportand/or encompass one, two or more vessels. There may be variations andalternatives to the embodiments described herein and that no singleembodiment should be construed to encompass the entire invention.

In one embodiment, a body 720 and/or support 730 may support one or morechannels 722 a, 722 b in a sample collection device. In one example, twochannels are provided, though descriptions relating to a two-channelembodiment may apply to any number of channels including but not limitedto 1, 3, 4, 5, 6 or more channels. Each of the channels may have a firstend 723 a, 723 b that may be a sample receiving end of the device. Thefirst ends of the respective channels may be open. The channels may beopen to ambient air. When the first ends of the channels contact afluid, such as blood, the fluid may be drawn into the channels. Fluidmay be drawn in via capillary action, or any other of the techniquesdescribed elsewhere herein. The fluid may travel along the length of thechannels to the respective second ends of the channels. The channels maybe fluidically segregated from one another. For example, a fluid mayenter a first channel 722 a via a first end 723 a, pass through thelength of the channel, and exit the first channel at the second end.Similarly, fluid may enter a second channel 722 b via a first end 723 b,pass through the length of the channel, and exit the second channel atthe second end. The first and second channels may be fluidicallysegregated so that fluid from the first channel does not pass into thesecond channel and vice versa. In some embodiments, the fluid may passto the second ends of the channels without exiting initially.

The channels 722 a, 722 b may have a parallel configuration. Forexample, the first ends 723 a, 723 b of the channels may be about thesame distance apart as the second ends of the channels. The first endsof the channels may or may not be in contact with one another.

A support 730 may have one or more optical indicators, such as opticalwindows 732 a, 732 b. The optical windows may be positioned over thechannels 722 a, 722 b. In some instances, the optical windows may bepositioned over portions of the channels. A single window may provide aview to a single channel portion or to multiple channel portions. In oneexample, the same number of optical windows may be provided as channels.Each optical window may correspond to a respective channel. Both theoptical window and channels may be formed of an optically transmissivematerial that may permit a user to view whether a sample has reachedand/or passed through the underlying portion of the channel from outsidethe sample collection device. Such determination may be useful indetermining when to compress the sample collection device.

A base 740 may be connected to a support 730 of the sample collectiondevice. The base may or may not directly contact the support. The basemay be fixed relative to the support during use of the device. In someinstances, the base may be removable from the support. A portion of thebase may be insertable into the support and/or vice versa. In someembodiments, the base may slide out from the support in a longitudinaldirection relative to the support. In some instances, the base may slideco-axially with the support without rotating. In some instances, a basemay rotate while moving relative to the support.

The base 740 may be capable of supporting one or more vessels 746 a, 746b. The base may have a housing that may at least partially surround theone or more vessels. In some instances, the vessels may be completelysurrounded when the base is engaged with a support 730. The height ofthe base may extend beyond the height of the vessels. Alternatively, theheight of the base may extend to the same degree or less than the heightof the vessels. The base may have one or more indentation, protrusion,groove, or shaped feature to accept the vessels. The base may be formedwith a shape that is complementary to the shape of the vessels. Forexample, the base may have one or more tube shaped indentation intowhich tube shaped vessels may snugly fit. The vessels may friction-fitinto the base. The vessels may be maintained in an upright positionrelative to the base. There may be variations and alternatives to theembodiments described herein and that no single embodiment should beconstrued to encompass the entire invention.

The same number of vessels may be provided as the number of channels.For example, if N channels are provided, then N vessels may be provided,wherein N is a positive whole number (e.g., 1, 2, 3, 4, 5, 6, 7, 8, ormore). Each channel may correspond to a respective vessel. In oneexample, a sample collection device may have a first channel and asecond channel, as well as a respective first vessel and second vessel.A first channel 722 a may be in or may be configured to be brought intofluid communication with a first vessel 746 a, and a second channel 722b may be in or may be configured to be brought into fluid communicationwith a second vessel 746 b.

In some embodiments, each vessel may have a body 749 a, 749 b and a cap748 a, 748 b. The vessels may have any features or characteristics asdescribed elsewhere herein.

A base 740 may have one or more optical indicators, such as opticalwindows 742 a, 742 b. The optical windows may be positioned over thevessels 746 a, 746 b. In some instances, the optical windows may bepositioned over the vessel bodies. A single window may provide a view toa single vessel or to multiple vessels. In one example, the same numberof optical windows may be provided as vessels. Each optical window maycorrespond to a respective vessel. Both the optical window and vesselsmay be formed of an optically transmissive material that may permit auser to view whether a sample has reached the vessel from outside thesample collection device. Such visual assessment may be useful indetermining when the sample has reached the vessels, and when the basecan be removed from the sample collection device.

One or more engagement assemblies may be provided. The engagementassembly may include a channel holder 750 and/or a force-exertingcomponent, such as a spring 752 or elastic. In one embodiment, theholder 750 may keep the adaptor channel 754 affixed to the support. Aswill be described elsewhere herein, the adaptor channel 754 may beformed integrally with the collection channel or may be a discreteelement that may be a stand-alone piece, part of the collection channel,or part of the vessel. In one embodiment, the holder 750 may prevent theadaptor channel 754 from sliding relative to the support. The holder 750may optionally provide a support upon which a force-exerting component,such as a spring, may rest.

In one example, the engagement assemblies may include a spring 752 whichmay exert a force so that the body 720 is at an extended state, when thespring is at its natural state. When the body is at its extended state,space may be provided between the vessels 746 a, 746 b and theengagement assemblies. When a body is in its extended state, theinterior portion 729 of the body may be exposed and/or uncovered by thesupport 730. In some instances, when the body is in its extended state,the second ends of the channels 722 a, 722 b may or may not contact thecaps of the vessels. The second ends of the channels may be in aposition where they are not in fluid communication with the interiors ofthe vessels. There may be variations and alternatives to the embodimentsdescribed herein and that no single embodiment should be construed toencompass the entire invention.

A sample collection device may have any number of engagement assemblies.For example, the same number of engagement assemblies may be provided asnumber of channels. Each channel may have an engagement assembly. Forexample, if a first channel and a second channel are provided, a firstengagement assembly may be provided for the first channel, and a secondengagement assembly may be provided for the second channel. The samenumber of engagement assemblies and vessels may be provided.

FIGS. 8A-8B provide an example of a sample collection device 800 havingchannels 822 a, 822 b that are in fluid communication with the interiorof vessels 846 a, 846 b within the device. The sample collection devicemay include a body 820, support 830, and base 840. The body and/orsupport may support and/or encompass at least a portion of one, two ormore channels. The channels may extend beyond an end of the body. Thebase may support and/or encompass one, two or more vessels.

In one embodiment, a body 820 and/or support 830 may support one or morechannels 822 a, 822 b in a sample collection device. For example, afirst channel and second channel may be provided. Each of the channelsmay have a first end 823 a, 823 b that may be provided at a samplereceiving end of the device that may extend beyond the body. The firstends of the respective channels may be open. The channels may be open toambient air. The channels may be rigid or may be flexible. In someembodiments, the channels may have a length that may permit them to bebent into contact with one another. When the first ends of the channelscontact a fluid, such as blood, the fluid may be drawn into thechannels. Each channel end may be separately contacted to a fluid, whichis drawn into the respective channel. This may involve angling thesample collection device so that only one opening into the channel is incontact with the sample fluid at any one time. Alternatively, allchannels may be simultaneously contacted to the same sample which issimultaneously drawn into the respective channels. Alternatively,multiple but not all channels may be simultaneously contacted to thesame sample which is then simultaneously drawn into the respectivechannels. The fluid may be drawn in via capillary action, or any otherof the techniques described elsewhere herein. The fluid may travel alongthe length of the channels to the respective second ends of thechannels. In some embodiments, the fluid may reach the second ends ofthe channels via capillary action or other techniques described herein.In other embodiments, the fluid need not reach the second ends of thechannels. The channels may be fluidically segregated from one another.

In some embodiments, the fluid may pass to the second ends of thechannels without exiting when the channels are not in fluidcommunication with the interiors of the vessels 846 a, 846 b. Forexample, the fluid may be drawn into the channel via capillary action,which may cause the fluid to flow to or near the end of the channelwithout causing the fluid to exit the channel.

The body 820 may be movable relative to the support 830 during use ofthe device. In some embodiments, the body may slide in a longitudinaldirection relative to the support. In one example, the body may have (i)an extended position where the channels are not in fluid communicationwith the interior of the vessels, and (ii) a compressed position wherethe channels are in fluid communication with the interior of thevessels. A sample collection device may be initially provided in anextended state, as shown in FIG. 7. After the sample has been collectedand flown through the length of the channel, a user may push the body into provide the sample collection device in its compressed state, asshown in FIG. 8. In some instances, when the body is in an extendedstate, an interior portion of the body is exposed. When the body is in acompressed state, the interior portion of the body may be covered by thesupport. A lip of the body may contact the support. Once the body hasbeen pushed in, the body may naturally remain pushed in, or may springback out to an extended state, once the pushing force is removed. Insome instances, a body may be pulled out to an extended state, or may bepulled out completely to provide access to vessels therein. Optionally,in some assemblies, removal of the body will not provide access to thevessels.

A base 840 may be connected to a support 830 of the sample collectiondevice. The base 840 may be capable of supporting one or more vessels846 a, 846 b. The base may have a housing that may at least partiallysurround the one or more vessels. In some instances, the vessels may becompletely surrounded when the base is engaged with a support 830. Thebase may have one or more indentation, protrusion, groove, or shapedfeature to accept the vessels. The base may be formed with a shape thatis complementary to the shape of the vessels. The vessels may bemaintained in an upright position relative to the base.

The same number of vessels may be provided as the number of channels.Each channel may correspond to a respective vessel. In one example, asample collection device may have a first channel and a second channel,as well as a respective first vessel and second vessel. A first channel822 a may be in or may be configured to be brought into fluidcommunication with a first vessel 846 a, and a second channel 822 b maybe in or may be configured to be brought into fluid communication with asecond vessel 846 b. The first channel may initially not be in fluidcommunication with a first vessel and the second channel may initiallynot be in fluid communication with the second vessel. The first andsecond channels may be brought into fluid communication with theinteriors of the first and second vessels respectively when the body ispushed in relative to the support. The first and second channels may bebrought into fluid communication with the first and second vesselssimultaneously. Alternatively, they need not be brought into fluidcommunication simultaneously. The timing of the fluid communication maydepend on the height of the vessel and/or the length of the channel. Thetiming of the fluid communication may depend on the relative distancesbetween the second end of the channel and the vessel.

In some embodiments, each vessel may have a body 849 a, 849 b and a cap848 a, 848 b. The vessel body may have a tubular shape. In someinstances, the vessel body may have a cylindrical portion. The bottom ofthe vessel may be flat, tapered, rounded, or any combination thereof.The vessels may comprise an open end and a closed end. The open end maybe a top end of the vessel, which may be at the end of the vessel closerto one or more channel. The closed end may be a bottom end of thevessel, which may be at the end of the vessel further from one or morechannel. There may be variations and alternatives to the embodimentsdescribed herein and that no single embodiment should be construed toencompass the entire invention.

A support 830 may have one or more optical indicators, such as opticalwindows 832 a, 832 b. The optical windows may be positioned overportions of the channels 822 a, 822 b. The optical windows may providean indicator of whether a sample has reached and/or passed through theportion of the channels shown by the optical windows. This may be usefulto assess whether the sample has flowed sufficiently for the user topush the body into the sample collection device. In some instances, itmay be desirable for the sample to reach the second end of the channels,or to near the second end of the channels, before causing the channelsto enter into fluid communication with the vessels. In some instances,the sample may need to reach a certain portion of the channel beforepushing the body in to bring the channels into fluid communication withthe vessels. The certain portion of the channel may underlie the opticalwindows.

A base 840 may have one or more optical indicators, such as opticalwindows 842 a, 842 b. The optical windows may be positioned over thevessels 846 a, 846 b. In some instances, the optical windows may bepositioned over the vessel bodies. The optical windows may provide anindicator of whether a sample has entered the vessels. The opticalwindows may show how much sample has filled the vessels. This may beuseful to assess whether a sufficient amount of sample has entered thevessels. In some instances, it may be desirable for a particular amountof sample to enter the vessels before removing the vessels from fluidcommunication with the channels. A predetermined volume of sample in thevessels may be desired before removing a base of the device, therebybringing the vessels out of fluid communication with the channels.

The vessels and/or interfaces with the channels may have anycharacteristic or feature, such as those described elsewhere herein. Insome instances, a second end of the channel may penetrate a cap of thevessel, thereby bringing the channel into fluid communication with thevessel. In some instances, the channel may be withdrawn from the vessel,and the cap of the vessel may form a fluid-tight seal, therebypermitting a fluid-tight environment within the vessel when the channelis brought out of fluid communication with the vessel.

One or more engagement assembly may be provided. The engagement assemblymay include a channel holder and/or a force-exerting component, such asa spring or elastic. The holder may keep the channel affixed to thebody. The holder may prevent the channel from sliding relative to thebody. The holder may optionally provide a support upon which aforce-exerting component, such as a spring, may rest.

In one example, the engagement assemblies may include a spring which mayexert a force so that the body is at its extended state, when the springis at its natural state. When the body is at its extended state, spacemay be provided between the vessels 846 a, 846 b and the bottom portionof the sample body 820. The second ends of the channels may be in aposition where they are not in fluid communication with the interiors ofthe vessels.

When the body is pressed in, the spring 852 may be compressed (see alsoFIGS. 9A-9C). The second ends of the channels may penetrate the caps ofthe vessels. The second ends of the channels may enter the interior ofthe vessel. In some instances, a force may be provided to drive thefluid from the channels into the vessels. For example, a pressuredifferential may be generated between the first and second ends of thechannels. A positive pressure may be provided at the first end 823 a,823 b of the channels and/or a negative pressure may be provided at thesecond end of the channels. The positive pressure may be positiverelative to the pressure at the second end of the channel, and/orambient air. The negative pressure may be negative relative to thepressure at the first end of the channel and/or ambient air. In oneexample, the vessels 846 a and 846 b may each have a vacuum therein.When the second end of a channel penetrates a vessel, the negativepressure within the vessel may suck the sample into the vessel. Inalternative embodiments, the sample may enter the vessel driven bycapillary forces, gravity, or any other motive force. Optionally, theremay be single or multiple combinations of forces to fill the vessel withfluid.

In some instances, different types of motive forces may be used to drawthe sample into the channel, and from the channel into the vessel. Forexample, a capillary force may draw the sample into a channel, and apressure differential may drive the sample from the channel into thevessel. Any combinations of motive forces may be used to draw sampleinto the channel and into the vessel.

Some time may elapse after a sample has been introduced to a channel fortraveling along the length of the channel. A user may introduce a sampleto the sample collection device and may wait for the sample to travelthe length of the channel. One or more optical indicator along thelength of the channel may be provided, which may indicate whether thesample has reached the end of the channel. In other embodiments, theuser may wait a predetermined amount of time before pushing in the body.The body may be pushed in after the user has determined the sample hastraveled a sufficient length of the channel and/or a sufficient amountof time has passed since the sample was introduced. The body may have aflat surface which may be easy for the user to push. In some instances,the flat surface may have a cross-sectional area that may be sufficientfor a user's fingers to press down on the body. After the body is pushedin, the channels may be brought into fluid communication with thevessels, and sample may flow from the channel into the vessels. Anoptical indicator may be provided so that a user may know when thevessels have been filled.

Once the vessels have been filled, they may be transferred to a desiredlocation, using systems and methods described elsewhere herein. Aspreviously described, the entire sample collection device may betransferred. In other embodiments, the base portion may be removablefrom the rest of the device. In one example, the base may be removedfrom the sample collection device, and the vessels may be transferredalong with the base. Alternatively, the base may be removed from thesample collection device to provide access to the vessels, and thevessels may be removed from the device and transmitted

Referring now to FIGS. 9A-9C, examples of a sample collection device 900and method of use will now be described. In one nonlimiting example, thedevice may have a body 920, support 930, and base 940. The body 920,support 930, and base 940 may be movable relative to one another. Insome instances, the various components of the devices may be movableduring different stages of use. Examples of stages of use may includewhen the device is in an extended state, compressed state, and separatedstate.

FIG. 9A shows an example of the device 900 in an extended state. Thebody 920 may be extended relative to the support. Channels 922 a, 922 bconfigured to transport a sample may be affixed to the body. A first endof a channel may extend out from the body and/or the rest of the samplecollection device. A second end of the channel may be within and/orencompassed by a portion of the sample collection device. The channelmay be fluidically isolated from a respective vessel housed by the base940. The support 930 may be positioned between the body and base. Thesupport may at least partially encompass a portion of the channel. Insome instances, the support may encompass the second end of the channel.

When in an extended state, the device may have an extended length. Thelength of the device may be from the bottom of the base to the first endof the channels. Alternatively, the length of the device may be measuredfrom the bottom of the base to the top of the body.

As seen in FIG. 9A, the device 900 may be in an extended state when thesample is introduced to the device. For example, a sample may becontacted by at least a first end of a channel. The sample may be drawninto the channel via capillary action or any other technique or motiveforce described herein. The forces may act alone or in combination todraw sample into the device. The device 900 may remain in an extendedstate while the sample is traversing the channel. The sample may fillthe entire length of the channel, a portion of the length of thechannel, or at least a minimum portion to meet a desired sampleacquisition volume.

FIG. 9B shows an example of the device 900 in a compressed state. Thebody 920 may be compressed relative to the support. The channels 922 a,922 b may be affixed to the body. The channels may be fluidiccommunication with their respective vessels. When the device is broughtinto a compressed state, a first channel may be brought into fluidcommunication with an interior of a first vessel, and a second channelmay be brought into fluid communication with an interior of a secondvessel.

By way of nonlimiting example, a user may push the body 920 toward thesupport 930 (or vice versa) to bring the device into a compressed state.The relative motion between parts may involve movement of both pieces.Optionally, movement may involve moving only one of them. In the presentexample, the body 920 may be pushed all the way to the support 930 sothat no interior portion of the body is exposed and/or a lip of the bodycontacts the support. Any stop mechanism may be used that may be engagedwhen the device is completely compressed. Alternatively, the body mayonly be partially pushed. For example, a portion of the interior portionof the body may be exposed. The support may be positioned between thebody and base. The support may at least partially encompass a portion ofthe channel. In some instances, the second end of the channel may extendbeyond the support of the device.

When in a compressed state, it should be understood that the device 900may have a compressed length. The length of the device 900 may be fromthe bottom of the base to the first end of the channels. Alternatively,the length of the device may be measured from the bottom of the base tothe top of the body. The compressed length of the device may be lessthan the extended length of the device. In some embodiments, thecompressed length of the device may be at least about 0.1 cm, 0.5 cm,1.0 cm, 1.5 cm, 2.0 cm, 2.5 cm, 3.0 cm, 3.5 cm, 4.0 cm, or 5.0 less thanthe extended length of the device. The compressed length of the devicemay be less than or equal to about 50%, 60%, 70%, 75%, 80%, 85%, 90%,95%, 97% or 99% of the extended length of the device.

One or more engagement assemblies may be provided with the device 900.The engagement assembly may include a channel holder 950 and/or aforce-exerting component, such as a spring 952 or elastic. The holder950 may keep the adaptor channel 954 affixed to the support. As will bedescribed elsewhere herein, the adaptor channel 954 may be formedintegrally with the collection channel or may be a discrete element thatmay be a stand-alone piece, part of the collection channel, or part ofthe vessel. In one embodiment, the holder 950 may prevent the adaptorchannel 954 from sliding relative to the support. The holder 950 mayoptionally provide a support upon which a force-exerting component, suchas a spring, may rest. The force-exerting component, such as a springmay be in a compressed state when the device is in a compressed state.The spring may exert a force on the body of the device when the deviceis in a compressed state.

The device may be in a compressed state when the sample is transferredfrom the channels to the respective vessels. In some examples, thetransfer may occur via pressure differential between the channels andthe interiors of the vessels, when they are brought into fluidiccommunication. For example, a second end of the channel may be broughtinto fluidic communication with the interior of the vessel. The vesselmay have a vacuum and/or negative pressure therein. The sample may besucked into the vessel when the channel is brought into fluidiccommunication with the vacu-vessel. The device may remain in acompressed state while the sample is being transferred to the vessel.The sample may fill the entire vessel or a portion of the vessel. Theentirety of the sample (and/or greater than 90%, 95%, 97%, 98%, 99%,99.5% or 99.9% of the sample) from the channels may be transferred tothe vessels. Alternatively, only a portion of the sample from thechannels may be transferred to the vessels.

Referring now to FIG. 9C, an example of a device 900 in a separatedstate will now be described. The base 940 may be separated from the restof the device 900. The body 920 may be extended or compressed relativeto the support 930. In one example, the extended state may be thenatural state, so that when the force is no longer exerted on the bodyby the user, the body may extend back to the extended state. Thechannels 922 a, 922 b may be affixed to the body.

When the device 900 is in a separated state, the base 940 may beseparated from the support 930 of the device. The channels 922 a, 922 bmay be removed from fluidic communication with their respective vessels946 a, 946 b. When the device 900 is brought into the separated state, afirst channel may be brought out of fluid communication with an interiorof a first vessel, and a second channel may be brought out of fluidcommunication with an interior of a second vessel. This may occursequentially or simultaneously. When the channels are removed from thevessels, the vessels may assume a sealed state to prevent undesiredmaterial from entering the vessels. In some embodiments, the vessels maybe fluid-tight after removal of the channels. Optionally, the vesselsmay be gas-tight after removal of the channels.

A user may separate the base 940 from the support 930 to bring thedevice into a separated state to remove the vessels therein. In someembodiments, the base may be separated from the support or vice versa.Separating the base from the support may expose the vessels 946 a, 946 bthat are supported by the base. The vessels may be press-fit orotherwise held within the base. The vessels 946 a, 946 b may beremovable from the base. By way of non-limiting example, removing thevessels 946 a, 946 b allows them to be placed with other vessels in aclimate controlled transport container for transport to a receiving sitesuch as but not limited to an analysis site. Optionally, the vessels 946a, 946 b may be removed to allow for pre-treatment such as but notlimited to centrifugation prior to being sent on for processing at areceiving site such as but not limited to an analysis site.Alternatively, the vessels 946 a, 946 b may remain with the base.

FIGS. 10A-10B provide additional views of a sample collection device1000 in a separated state. When in a separated state, the base 1040 maybe separated (partially or completely) from the support 1030 and/or body1020 of the device. This allows for the removal of the vessels 1046 aand 1046 b through the end of base 1040 previously not externallyexposed when the device 1000 was not in a separate state.

When the device is in a separated state, one or more channels 1022 a,1022 b may be fluidically isolated from one or more vessels 1046 a, 1046b housed by the base 1040. The vessels may be fluidically sealed fromtheir environment. The vessels may contain sample therein, that had beentransported through the collection channels, reached a minimum filllevel, and then substantially fully deposited into the respectivevessels. The base 1040 may include one or more optical indicator 1046 a,1046 b. The optical indicator may show a portion of the vessels thereinsuch that the device 1000 is not moved into the separate state until aminimum fill level has been reached in the vessels. By way ofnon-limiting example, the vessels may have an optically transmissivematerial that may permit a user to view the sample within the vesselsfrom outside the base.

In some embodiments, the base 1040 may encompass at least a portion ofthe vessels. The base may have a hollow interior and walls surroundingthe hollow interior. The base may have one or more shaped feature thatmay support the vessels. The vessels may be provided within the hollowinterior. The walls may surround the vessel. The base may have an opentop though which the vessels may be exposed. The vessels may or may notbe removed through the open top.

Collection Device with Multiple Collection Channels

Referring now to FIGS. 11A-11F, a still further embodiment as describedherein will now be described. This embodiment provides a bodily fluidsample collection device 1100 for use in collecting a fluid sample thatmay be pooled or otherwise formed on a surface, such as but not limitedto the skin or other target area of a subject. Although this embodimentshows a device body which defines at least two collection channels ofdifferent volumes therein, it should be understood that devices withfewer or greater numbers of collection channels are not excluded.Embodiments where the same collection volume is used for one or more thechannels are also not excluded. There may be variations and alternativesto the embodiments described herein and that no single embodiment shouldbe construed to encompass the entire invention.

FIG. 11A shows a perspective view of one embodiment of a bodily fluidsample collection device 1100 with a distal end 1102 configured toengage a fluid sample on a surface. In this embodiment, the distal end1102 may have a configuration designed to better engage a droplet orpool of bodily fluid or sample formed on a surface. Some embodiments, inaddition to a desired shape, may also have surface treatments at thedistal end 1102, such as but not limited to, chemical treatments,texturing, surface features, or coatings to encourage fluid flow towardsthe one or more openings 1104 and 1106 on the distal end 1102 leading tothe channels in the device 1100.

As seen in FIG. 11A, this embodiment of the sample collection device1100 has two openings 1104 and 1106 for receiving the sample fluid. Itshould be understood that some embodiments may have more than twoopenings at the distal end. Some embodiments may only have one openingat the distal end. Optionally, some embodiments may have additionalopenings along a side or other surfaces leading away from the distal end1102 of the device 1100. The openings 1104 and 1106 may have anycross-sectional shape. In some non-limiting examples, the openings mayhave a circular, elliptical, triangular, quadrilateral (e.g., square,rectangular, trapezoidal), pentagonal, hexagonal, octagonal, or anyother cross-sectional shape. The cross-sectional shape may remain thesame or may vary along the length of the collection device body. In someinstances, the openings may have a cross-sectional area of less than orequal to about 2 mm², 1.5 mm², 1 mm², 0.8 mm², 0.5 mm², 0.3 mm², or 0.1mm². Some embodiments have the opening be the same shape. Others may usedifferent shapes for the one or more openings.

The sample fill portion 1120 which may be the body of the samplecollection device 1100 may be formed from a transparent and/ortranslucent material that may enable a user to see if a sample hasentered sample collection channel(s) (see FIG. 11B) in the sample fillportion 1120. In some embodiments, the entire sample fill portion 1120is transparent or translucent. Alternatively, some embodiments may onlyhave all areas over the channel or only select portions of the channelor sample fill portion 1120 be transparent or translucent to allow auser to visualize the filling of sample into the sample collectiondevice 1100. Optionally, the sample fill portion is made of an opaquematerial but has an opening or a window to allow for visualization offill level therein. The device 1100 may further include one or morevisualization windows 1112 and 1114 to allow a user to see when adesired fill level has been reached. The visualization window may beformed from a transparent and/or translucent material. Alternatively,the visualization window may be an opening without any material therein.Additional visualization windows can also be used to determine of all ofthe fluid in the collection channels have been emptied into the vessels1146 a and 1146 b (see FIG. 11B).

FIG. 11A also shows that some embodiments of support 1130 may haveoptical windows 1132 and 1134 which are positioned to show fill levelsin the vessels 1146 a and 1146 b to show if the vessels in base 1140have been moved into position to receive sample fluid. Optionally, thewindows 1132 and 1134 may be cutouts that act as guides for the snapfeature of based in order to define the start and end positions duringactivation. It should be understood that the base can be configured tohold one or more sample vessels. By way of example and not limitation,the entire base 1140 can be removed from the sample collection devicebefore or after sample fill. The base 1140 can be used as holder toretain the sample vessels therein during transport, and in such anembodiment, the base 1140 along with the sample vessels would be loadedinto a shipping tray or other holder for transport. Alternatively, someembodiments may remove the sample vessels from the base 1140 and thentransport the vessels without the base 1140 holding them.

FIG. 11B shows a cross-sectional view along section lines B-B of theembodiment shown in FIG. 11C. FIG. 11B shows the channels 1126 and 1128in the portion 1120. The sample fill portion 1120 may be formed from twoor more pieces which join together to define the portion 1120. Some maydefine the channels in one piece and then have another piece which matesto the first piece to define an opposing or top wall surface of thechannel. In terms of manufacturing, this allows one piece to havechannels molded or otherwise formed into the body and the opposing piecewill mate to act as a cover for the channels or may also includeportions of the channel too. The channels 1126 and 1128 may be formedonly in portion 1120 or may also extend into support 1130 that hasfeatures to connect with the vessels held in base or carrier 1140. Someembodiments may integrally form portions 1120 and 1130 together. Support1130 may also be configured to hold adapter channel 1150 which willfluidically connect the channels 1126 and 1128 with their respectivevessels 1146 a and 1146 b.

Although these embodiments herein are described using two channels andtwo vessels, it should be understood that other numbers of channels andvessels are not excluded. Some embodiments may have more channels thanvessels, wherein some channels will couple to the same vessel. Someembodiments may have more vessels than channels, in which case multiplevessels may operably couple to the same channel.

As seen in FIG. 11B, the channels 1126 and 1128 may be of differentsizes. This allows for different fluid volumes to be collected in eachchannel before they are simultaneously transferred into the vessels 1146a and 1146 b. Optionally, some embodiments may have the channels 1126and 1128 sized to contain the same volume of fluid. In some embodiments,the fluid pathway of the channels 1126 and 1128 are shaped and/or angledso that openings near the distal end 1102 are closer together thanproximal ends, which may be further apart to align them for entry intothe vessels 1146 a and 1146 b. There may be variations and alternativesto the embodiments described herein and that no single embodiment shouldbe construed to encompass the entire invention.

FIG. 11B also shows that some embodiments may use needles for theadapter channels 1150 and 1152 in the body 1130 which are incommunication with the channels 1126 and 1128. The needles each has achannel to allow for fluid to pass therethrough from the collectionchannels 1126 and 1128 to the ends of the needles. As seen in FIG. 11B,the vessels 1146 a and 1146 b in the base 1140 are slidable relative tothe support 1130 as indicated by arrow 1156. Relative motion betweensupport 1130 and base 1140 can close the gap 1154. Closing the gap 1154brings the adapter channels 1150 into the cap 1148 a of the vessel 1146a until there is fluid communication between the interior of vessel 1146a and the collection channel 1126. At that time, motive force in theform will then move fluid in the channel 1126 into the vessel 1146 a.

By way of example and not limitation, any combinations of motive forcesmay be used to draw sample into the vessel. Some embodiment may use pullfrom vacuum in the vessels 1146 a to draw sample into the vessel. Somemay use pushing force from external pressure to move fluid into thevessel. Some embodiments may use both. Some may rely on capillary and/orgravity. In some embodiments, the motive force(s) used to draw sampleinto the channel is different from motive force(s) used to draw sampleinto the vessel. In some alternative embodiments, the motive force(s)may be the same for each stage. In some embodiments, the motive force(s)are applied sequentially or at defined time periods. By way ofnon-limiting example, motive force(s) to draw sample into the vessel isnot applied until the at least one channel has reach a minimum filllevel. Optionally, motive force(s) to draw sample into the vessel is notapplied until the at least two channels have each reach a minimum filllevel for that channel. Optionally, motive force(s) to draw sample intothe vessel is not applied until all channels have each reach a minimumfill level for that channel. In some embodiments, the motive force(s)are applied simultaneously. This features recited may be applicable toany of the embodiments herein.

Referring now to FIG. 11E, an enlarged cross-sectional view of thedevice 1100 is shown. This embodiment shows that the support 1130 has alip portion 1136 sized to extend over the adapter channels 1150 and 1152in an amount sufficient to prevent a user from inserting a finger intothe gap 1154 and piercing the finger on one of the needle.

Additionally, as shown in FIGS. 11B and 11E, the present embodiment hasat least two channels in the sample collection device 1100. This allowsfor each of the channels 1128 and 1126 to each introduce a differentmaterial into the sample. By way of non-limiting example, if the sampleis whole blood, one channel can introduce heparin into the blood whileanother channel introduces ethylenediaminetetraacetic acid (EDTA). Notonly do these anti-coagulants prevent premature clogging of the channelsduring fill, but also introduce anti-coagulant into the whole blood inpreparation for transport in the vessels 1146 a and 1146 b. Optionally,the channel(s) may also be plasma coated in addition to or in place ofthe anti-coagulants. The plasma coating can reduce the flow resistanceof the body fluid sample in the channels. Such a coating can be appliedin patterns such as but not limited to strips, rings, or other patternsalong with any other coating(s) to be used in the channels.

Optionally, there is sufficient quantity of anti-coagulant in therespective channel such that the sample fluid will contain a desiredlevel of anti-coagulant in the sample fluid after only a single pass ofthe fluid through the channel. In traditional blood vials, the bloodsample does not contain anti-coagulant until it enters the vial and oncein the vial, the technician typically repeatedly tilts, shakes, and/oragitates the vial to enable mixing of anti-coagulant in the vials. Inthe present embodiment, the sample fluid will contain anti-coagulantprior to entering the sample vessel and it will do so without having torepeatedly tilt or agitate the sample collection device. In theembodiment herein, a single pass provides enough time and sufficientconcentration of additive such as anti-coagulant into the sample fluid.In one embodiment, an EDTA channel has a volume of 54 uL coated by 200mg/mL EDTA; a channel for Heparin has a volume of about 22 uL coated by250 units/mL Heparin. In another embodiment, the EDTA channel has avolume of 70 uL coated by 300 mg/mL EDTA; the channel for Heparin has avolume of about 30 uL and is coated by 250 units/mL Heparin. By way ofnon-limiting example, a channel of volume from 50 to 70 μL can be coatedby EDTA in the range from about 200 to 300 mg/mL EDTA. Optionally, achannel of volume from 70 to 100 μL can be coated by EDTA in the rangefrom about 300 to 450 mg/mL EDTA. Optionally, a channel of volume from20 to 30 μL can be coated by Heparin in the range from 250 units/mLHeparin. By way of example, the material may be solution coated onto thetarget surface for less than 1 hour and then dried overnight. There maybe variations and alternatives to the embodiments described herein andthat no single embodiment should be construed to encompass the entireinvention.

Referring now to FIG. 11G, a still further embodiment will now bedescribed. The embodiment of FIG. 11G shows that at a distal end 1202 ofthe sample collection device 1200, instead of having one opening 1204for each of the channels, the sample collection device 1200 merges twoor more of the channels into a single channel. The embodiment of FIG.11G shows that there is common channel portion prior to the split of thecommon channel into to a plurality of separate channels. As will bedescribed below in FIG. 11I, optionally, there may be back flowpreventer such as but not limited to a vent positioned along theseparate channel to reduce the possibility of drawing sample from onechannel into another channel during filling and/or extraction of samplefrom the channels into the sample vessel(s).

As seen in FIG. 11H, this use of common flow paths can result in areduced number of openings on the exterior of the sample collectiondevice 1200, which may make it align the opening 1204 to engage thebodily fluid sample. It may also increase the capillary force fordrawing bodily fluid sample into the sample collection device 1200 byhaving more capillaries pulling on the same channel where the bodilyfluid sample enters the collection device.

Referring now to FIG. 11I, a cross-sectional view of select componentsof a sample collection device will now be described. FIG. 11I shows thatthe sample collection device can have two channels 1182 and 1184 thathave a common portion 1186 leading towards an inlet opening on thedevice. In some embodiments, the common portion 1186 is a continuationof one of the channels 1182 or 1184 in terms of size, shape, and/ororientation. Optionally, the common portion 1186 is not of the samesize, shape, and/or orientation of any of the channels 1182, 1184, orany other channel that may be in fluid communication with the commonportion 1186. FIG. 11I shows that in one non-limiting example, there maybe a step at the interface 1188 between the channel 1182 and 1184. Thisinterface 1188 may be configured to ensure flow into both of thechannels so that they will both reach a full fill. In one embodiment,the interface 1188 has a size greater than the channel 1182 leading awayfrom the interface 1188. Although other sizes are not excluded, thisinterface 1188 of greater size may ensure that sufficient flow willenter the channel 1182, which in the present embodiment, has a smallerdiameter and reduced volume relative to the channel 1184. There may bevariations and alternatives to the embodiments described herein and thatno single embodiment should be construed to encompass the entireinvention.

FIG. 11I also shows that there may be vents 1190 and 1192 that can beused to prevent cross-flow between channels, particularly when sample isbeing transferred into the sample vessels. In one embodiment, the vents1190 and 1192 are open at all times. In another embodiment, the vents1190 and 1192 may be open only at select times, such as but not limitedto after the channels 1182 and 1184 are filled or substantially filled.Some embodiments may use a dissolvable material the plugs the vents 1190and 1192 until they are in contact with sample fluid. Optionally, someembodiments may use a slidable covers one or more of the vents 1190 and1192 such that they are only opened at times selected by the user. Inone embodiment, the covers are linked to the sample vessels such thatmovement of the sample vessels to move into fluid communication with thechannels will also open one or more vents 1190 and 1192 to reduce therisk of cross-flow between channels. Optionally, other anti-crossflowmechanisms such as but not limited to valves, gates, or plugs can alsobe used to prevent fluid transfer between channels 1190 and 1192.

FIG. 11I also shows that there may be anti-leakage devices 1194positioned over the adapters 1150 and 1152. In this embodiment, theanti-leakage devices 1194 are frits which may be slidably moved from afirst position where they prevent sample from leaking out from theadapters 1150 and 1152 to a second position wherein they allow theadapters to deliver fluid into the sample vessels. In one non-limitingexample, the anti-leakage devices 1194 will slide when they are engagedby the sample vessels or the housing that holds the sample vessels. Themovement of the sample vessels or the housing in this non-limitingexample shows that the movement of those elements will also causemovement of the anti-leakage devices 1194.

Referring now FIG. 11J, yet another embodiment of a sample collectiondevice 1160 will now be described. This embodiment of the samplecollection device 1160 shows that the device 1160 has a sample entrylocation 1204 that leads to a plurality of channels 1162 and 1164 in thedevice 1160. Although FIG. 11J show that the channels 1162 and 1164 mayhave different shapes and/or sizes, some embodiments may be configuredto have the same volumes and/or shapes. It should also be understoodthat the sample entry location 1204 can be on the surface of the device1160, or optionally, it can be part of a tip, nozzle, stub, or otherprotrusion that extends from the body of the device 1160. Thisprotrusion may be in the same plane and aligned parallel with the bodyof the device or optionally, it may be angled so that the axis of theprotrusion intersects the plane of the device 1160.

FIG. 11J further shows that for some embodiments, there may be sampleflow features 1166 and 1168 to draw or otherwise preferentially directsample in a desired direction. In some embodiments, the features 1166and 1168 are guides that operate to decrease channel dimension in atleast one axis, such as but not limited to width or height, and thusincrease capillary action through those areas of reduced dimension. Inone non-limiting example, these flow features 1166 and 1168 can assistfluid flow through the channel areas positioned near the anti-crossflowfeatures 1170 during sample entry into the channels. In one embodiment,the flow features 1166 and 1168 are sized so as to preferentiallyimprove flow in the inbound direction when flow is drawn primarily bycapillary action. Outbound flow, in one scenario, is not based oncapillary force but on vacuum pulling force (such as from an adjacentchannel), and these flow features 1166 and 1168 of the presentembodiment are not configured to provide assistance under those vacuum,non-capillary flow conditions. Thus, some but not all embodiments offlow features 1166 and 1168 are configured to assist under at least onetype of flow condition but not certain other flow condition(s).Optionally, some embodiments may use other techniques alone or incombination with the guides, such as but not limited to, shapedfeatures, hydrophobic material(s), hydrophilic material(s), or othertechniques to push/pull samples towards a desired location.

FIG. 11J also shows that in the one or more embodiments herein, theremay be angled side wall features 1167 that conically or otherwise narrowthe cross-sectional area of the channel in a manner that funnels sampleto minimize the amount of sample that may be retained in the channel andnot collected. FIG. 11J also shows that there may be locating feature(s)1169 to facilitate joining of parts together in a define location andorientation during manufacturing.

FIG. 11K shows a side view of this embodiment of the sample collectiondevice 1160. The side view of the device 1160 shows that there areembodiments where there are one or more anti-crossflow features 1170such as but not limited to vents to minimize undesired crossflow ofsample between the channels 1162 and 1164, particularly once a desiredfill level has been reached in the respective channels. Theanti-crossflow features 1170 and 1172 can prevent crossflow due to thebreak in fluid pathway created by the vents. The crossflow issuepresents itself most commonly when the vessels in the holder 1140 areengaged and provide an additional motive force to pull the sample fromthe channels into the vessels. This “pulling” effect may inadvertentlydraw sample from one channel to an adjacent channel. To minimizecrossflow, forces associated with pulling sample from the channel intothe vessel will pull from the vent and not fluid in an adjacent channel,thus minimizing undesired commingling of sample.

FIG. 11K also shows that in some embodiments herein, there may be commonportions 1130 and 1140 which can be adapted for use with differentsample fill portions 1120. Some may use different capillary fillportions 1120. Some embodiments may use fill portions that use differenttypes of capture techniques, such as but not limited to, samplesacquired from venous draws, arterial draws, or other sample drawn froman interior location or target site of the subject.

Referring now to FIG. 11L, one embodiment of the sample flow features1166 and 1168 are shown. This cross-sectional view of sample collectionportion with the channels 1162 and 1164 and the sample flow features1166 and 1168 near the common inlet pathway 1165 shows that the featuresare desired in one embodiment near where the sample is entering thechannels. FIG. 11L also shows, for channels of different volumes, it canbe desirable to position the inlet 1165 closer to the channel 1164 thathas the larger volume, as seen by the asymmetric location of inlet 1165.It can also be seen that in some embodiments, location(s) of the sampleflow features 1166 and 1168 can also be selected to control fillingrate, filling volume, or the like in the sample collection device 1160.It should be understood that one or more of features described can beadapted for use with other embodiments herein.

Referring now to FIG. 11M, channels 1162 and 1164 with sampleanti-crossflow features are shown. In one embodiment, the sampleanti-crossflow features are vents 1170 and 1172 located on at least onesurface of the channels 1162 and 1164. In one nonlimiting example, thesesample anti-crossflow features are located near any sample flow features1166 and 1168 in the device. In one embodiment, these anti-crossflowfeatures are configured to prevent flow between channels. Theseanti-crossflow features can be located near the maximum fill locationsof each of the channels such that as the channel is at or near itsmaximum sample capacity, the anti-crossflow features 1170 and 1172 arepositioned to prevent overfilled sample from causing sample that hasbeen treated in one channel from entering another channel andundesirably mixing samples from two channels together.

FIG. 11N shows a perspective view of the sample collection device 1160with sample fill indicators 1112 and 1114. In one embodiment, theseindicators 1112 and 1114 are openings or transparent portions of thedevice 1160 that allows for observation of at least one portion of thechannel(s) 1162 or 1164. When sample is visible in at least one of theindicators 1112 and 1114, it provides a cue to the user to then takeanother action such as but not limited to engaging the sample vessels inthe holder 1140. In some embodiments, there is only one sample fillindicator which is a proxy for sufficient fill of sample in two or moreof the channels. In some embodiments, the action to engage the samplevessels is only taken when indicated by indicators 1112 and 1114. Insome embodiments, the action to engage the sample vessels is only takenwhen indicated by only one of the indicators.

Referring now to FIGS. 11O, 11P, and 11Q, cross-section at variouslocations along one embodiment of the device 1160 in FIG. 11J are shown.FIG. 11O shows a cross-section showing the sample flow features 1166 and1168. The anti-crossflow features 1170 and 1172 are also shown.Engagement features 1174 can also be provided to enable mating of piecestogether to form the device 1160.

FIG. 11P shows that the adapter channels 1150 and 1152 are positioned toextend into or at least be in fluid communication with the samplechannels 1162 and 1164. Optionally, some embodiments may havemulti-lumen adapter channels 1150 or 1152. Optionally, some embodimentsmay have multiple adapter channels per sample channel, wherein suchadditional channels may be parallel to, angled, wrapped, or otherwiseoriented relatively to each other.

FIG. 11Q shows that in some embodiments, the vessel holder 1140 can beshaped asymmetrically (in the cross-sectional plane) or otherwise shapedto enable only one orientation that the holder 1140 can be received inthe device 1160. This can be particularly desirable when it is desiredto direct sample from a certain channel into a selected vessel. If theholder 1140 can be inserted in various orientations, the sample from onechannel may end up in the wrong vessel. Optionally, other features suchas alignment features, slots, visual cues, texture cues, and/or the likemay be used to encourage a preferred orientation of sample vessels inthe device.

Integrated Tissue Penetrating Member

Referring now to FIG. 11R, yet another embodiment of a sample collectiondevice will now be described. This sample collection device 1210comprises features similar to that shown in FIG. 11G, except that itfurther includes a tissue penetrating member 1212 that is mounted to thesample collection device 1210. An actuation mechanism 1214 such as butnot limited to a spring actuator can be used to launch the tissuepenetrating member. FIG. 11R shows the actuation mechanism 1214 in aresting state and that it can be a spring that can be compressed tolaunch a tissue penetrating member 1212 towards target tissue. Thetissue penetrating member 1212 can be housed inside a housing 1216(shown in phantom). In one embodiment, the housing 1216 comprises aportion that can be peeled back, pierced, released or otherwise openedto allow the tissue penetrating member 1212 to exit the housing but alsomaintain sterility of the tissue penetrating member 1212 prior to itsuse. In some embodiments, the portion may be a foil, a cap, a polymerlayer, or the like. There may be variations and alternatives to theembodiments described herein and that no single embodiment should beconstrued to encompass the entire invention.

In one embodiment, the tissue penetrating member 1212 path can becontrolled along both the “normal” (i.e., forward direction of thetissue penetrating member) and “orthogonal” (i.e., perpendicular to mainmotion vector) of the trajectory. Some embodiments may have not have ahard stop or bang stop at the deepest point of penetration (i.e., returnpoint), which is the main cause for spontaneous pain. Some embodimentsmay use a cushion, a cam pathway, or other non-hardstop mechanism toprevent pain associated with the shockwave of a sudden stop. Such ashockwave is detrimental even if the tissue penetrating membersuccessfully avoids hitting nerves near the wound location as theshockwave can activate such nerves even if direct contact was avoided.Optionally, some embodiments may have the tissue penetrating memberfollow a non-jitter path, to prevent a rough wound channel (residualpain). This may be achieved in some embodiments through tightertolerance in any guide pathway used with tissue penetrating member or apin associated with the tissue penetrating member. This may be anon-jitter path when penetrating the tissue. Optionally, this may be anon-jitter path for the tissue penetrating member both outside thetissue and when it is inside the tissue. This can reduce overall motion“wobble” of the tissue penetrating member that may cause residual pain,long-lasting trauma, and scarring.

Some embodiments may have a controlled outbound speed to prevent slowand delayed wound closure and after bleeding. By way of nonlimitingexample, the controlled outbound speed of the tissue penetrating membercan be controlled by mechanical mechanisms such as but not limited camsor higher friction materials.

Some embodiments may also include anti-bouncing mechanisms to preventunintended re-lancings that can be associated with an uncontrolledtissue penetrating member that rebounds into the tissue after initialwound creation. Some embodiments herein may have “parking” mechanisms orlock-out mechanisms that will engage the tissue penetrating member orits attachments to prevent re-entry of the tissue penetrating memberonce it has retracted out of the tissue or some other desired distance.

The abruptness with which the lancet comes to a stop in the skin atmaximum depth, before it starts its outbound motion and returning to itsstarting position, is an inherent issue of this design. With the lancetat its deepest point of penetration, the greatest amount of force isapplied to the skin. The drive mechanism simply bounces off the end ofthe device like a ball bounces back from the floor. The lancet, comingto an abrupt stop at the end point of its inbound motion, sends ashockwave into the skin, causing many pain receptors in the vicinity ofthe lancet to fire, even though they are not directly struck. Thisamplifies spontaneous pain substantially.

As mentioned, instead of simple spring actuated tissue penetratingmembers, some embodiments may use mechanical cam actuation. Devices withcam-actuation design can minimize “hard stopping” of the tissuepenetrating member. A cam mechanism is usually spring driven andgenerally offers a better guided actuation. The trajectory of the tissuepenetrating member is tightly controlled through a guided path of thetissue penetrating member holder via a pin riding in a cam. The cammechanism allows for a predetermined speed profile with a softer returnand distinct speed control for the tissue penetrating member outboundtrajectory. This mechanism also effectively avoids a bounce back of thelancet into the skin when the mechanism reaches its motion end point. Inaddition, the mechanical oscillation (or jitter/wobble) of the lancepath in both directions is reduced when fired in air. Some embodimentsherein may also minimize any mechanical wobble of the drive mechanism(e.g., due to uneven or rough cam slots) to prevent transfer of suchdrive mechanism wobble directly into the tissue because of its “forcedmotion profile.”

Optionally, some embodiments may use electronic actuation through anelectronically controlled drive mechanism. This technology uses aminiaturized electronic motor (e.g., voice coil, solenoid) coupled witha very accurate position sensor, moving the tissue penetrating memberinto and out of the skin with precisely controlled motion and velocity.Following rapid entry, the device decelerates the tissue penetratingmember to an exact, preset depth to return smoothly, without jitter, andrelatively slowly. This allows quick wound closure and avoids long-termtrauma. With this device, the force required to penetrate the lancetinto the skin is controlled while the tissue penetrating member isprogressing. The benefit of tightly controlling the tissue penetratingmember actuation “profile” is a reproducible painless lancing thatyields a sufficient and consistent blood sample for testing.

In terms of puncture site creation for blood sample extraction, it maybe desirable to elect the appropriate puncture site on one of thepatient's fingers (ring or middle) on their non-dominant hand. Thepuncture sites may be on the sides of the tips of the fingers. In onenonlimiting example, it may be desirable to hold the hand warmer stripagainst the patient's selected finger for 15 seconds. Optionally, somemay warm the patient's finger(s) from 10 to 60 seconds. Others may warmfor longer. The warming will increase blood flow to the target site. Toprepare the target site, it may be desirable to wipe the side tip of theselected finger or surface of the subject with an alcohol wipe orsimilar cleaning agent, being sure to wipe the selected puncture site.In some embodiments, it is desirable to wait until the skin iscompletely dry. Typically, one does not dry with gauze or blow air onthe fingertip to accelerate drying.

After a puncture has been formed, hold the finger downward, below thepatient's waist, in order to allow blood to flow. Massage the fingerlightly from base to tip until a blood drop has formed. Carefully fillthe blood collection device by touching the tip of the device to thebead of blood on the finger. Make sure the device is completely filled.Once the blood collection device is filled, press the bleeding area ofthe finger against the gauze pad on the table. Transfer the blood sampleinto the collection vessels. Place a bandage over the finger. Place thevessels with the sample into the shipping box inside the refrigerator.Discard all supplies in the biohazard sharps vessel. All supplies aresingle-use only.

If enough blood is not obtained from the first puncture, carefully placethe blood collection device on the table surface, ensuring that thedevice remains horizontal. Place a bandage over the finger that waspunctured. Select the appropriate puncture site on a different finger onthe patient's same hand. If the ring finger was punctured first, choosea new puncture site on the middle finger, and vice versa. Hold the handwarmer strip against the patient's selected finger for 60 seconds.Optionally, some may warm the patient's finger(s) from 30 to 90 seconds.This will increase blood flow to the finger. These techniques for bloodcollection using a sample collection device such as any of those hereincan enable sufficient sample collection of capillary blood for use inlaboratory testing at Clinical Laboratory Improvement Amendments (CLIA)certified facility and/or standards.

Referring now to FIG. 11S, yet another embodiment of a sample collectiondevice 1220 will now be described. In this embodiment, the tissuepenetrating member 1222 may be mounted at an angled relative to thesample collection device 1220. This angled configuration allows fortissue penetrating member to create a wound at a location that alignswith sample acquisition opening(s) 1103 and 1105. Although a standardspring-launched actuator is shown as the drive mechanism 1224 for thetissue penetrating member 1222, it should be understood that cam and/orelectrical drive systems may also be used in place of or in combinationwith the spring launcher. When the drive mechanism 1224 is a spring, thespring can be compressed to move the tissue penetrating member 1222 to alaunch position and the released to penetrate into the target tissue.FIG. 11S shows the tissue penetrating member 1222 in a resting position.Although the figures show a spring for the drive mechanism 1224, itshould be understood that other drive mechanism suitable for use inlaunching a tissue penetrating member to create a healable wound on asubject are not excluded. There may be variations and alternatives tothe embodiments described herein and that no single embodiment should beconstrued to encompass the entire invention.

A housing 1226, similar to that described for housing 1216, may beformed around the tissue penetrating member 1222. Although FIG. 11Sshows two tissue penetrating members 1222 mounted on the samplecollection device, it should be understood that devices with more orfewer tissue penetrating members are not excluded. For example, someembodiments may have only one tissue penetrating member 1222 mounted tothe sample collection device 1220. There may be variations andalternatives to the embodiments described herein and that no singleembodiment should be construed to encompass the entire invention.

Referring now to FIG. 11T, another embodiment of a sample collectiondevice 1230 will now be described. This embodiment shows that the tissuepenetrating member 1232 is contained within the sample collection device1230 and as seen in FIG. 11T, it is actually co-axially aligned with thecentral axis of the sample collection device. This positions the tissuepenetrating member 1232 to extend outward from the sample collectiondevice 1230 at a location close to where openings 1103 and 1105 arepositioned on the sample collection device 1230. Of course, deviceshaving more or fewer openings are not excluded and the embodiment ofFIG. 11T is exemplary and non-limiting. FIG. 11T shows that in oneembodiment of the sample collection device, a firing button 1234 may bemounted on the sample collection device 1230. Optionally, someembodiments may have the shaped front end 1236 function as the actuationbutton, wherein upon pressing the tissue against the front end 1236 to acertain depth and/or certain pressure, the tissue penetrating memberwill be actuated.

Once fired, the tissue penetrating member 1232 moves as indicated byarrow 1233. In some embodiments, the tissue penetrating member 1232 isfully contained inside the sample collection device 1230 prior toactuation. Some embodiments may have a visual indicator 1235 on thedevice 1230 to help guide the user on where the tissue penetratingmember 1232 will exit the device and where approximately the wound willbe formed.

In this non-limiting example, the entire device 1230 may be in a sterilepouch or package that is only opened before the device 1230 is used. Inthis manner, sterile conditions are maintained for the tissuepenetrating member and the collection device prior to use. This externalsterile pouch or package is also applicable to any of the otherembodiments herein. FIG. 11L also shows that a shaped front end 1236(shown in phantom) that can be integrally formed or separately attachedto the sample collection device 1230. This shaped front end 1236 canprovide suction to draw sample fluid into the sample collection device1230. Optionally, the shaped front end 1236 can be used to stretch thetarget tissue and/or force it into the shaped front end to applypressure to increase sample fluid yield from wound formed by the tissuepenetrating member 1232. It should be understood that any of theembodiments herein can be adapted to have a shaped front end 1236.Optionally, the shaped front end may have select hydrophobic area(s) todirect sample fluid to towards one or more collection areas on the frontend. Optionally, the shaped front end may have select hydrophilicarea(s) to direct sample fluid to towards one or more collection areason the front end.

Referring now to FIG. 11U, yet another embodiment of a sample collectiondevice will now be described. This embodiment is similar to that of FIG.11T except that, instead of single tissue penetrating member such as alancet, the embodiment of FIG. 11T uses a plurality of tissuepenetrating members 1242. In one embodiment, these tissue penetratingmembers are microneedles 1242 that are of reduced diameter as comparedto traditional lancets. A plurality of microneedles 1242 can besimultaneously actuated for device 1240 and create multiple wound siteson the tissue. The spacing of the microneedles 1242 can result in morecapillary loops being pierced and more channels being available forblood to reach the tissue surface. This also allows for a more “square”penetration profile as compared to a lancet which has a pointed tip anda tapered profile. This may enable the microneedles 1242 to engage morecapillary loops over a larger area without penetrating too deep intodeeper tissue layers that are more densely populated with nerve endings.

Referring now to FIGS. 11V and 11W, a still further embodiment of asample collection device will now be described. In the embodiment shownin these figures, the sample collection device 1100 may be mountedangled to a dedicated wound creation device 1250 that has a tissuepenetrating member 1252 configured to extend outward from the device1250. The sample collection device 1100, which may optionally beconfigured to have a shaped front end 1236 (with or without an openingto accommodate the tissue penetrating member 1252), can be removablymounted to the wound creation device 1250. Optionally, the samplecollection device 1100 may be flat mounted to the device 1250.Optionally, there may be a shaped cut-out on device 1250 for press-fitholding the sample collection device 1100. It should be understood thatother techniques for removably mounting the sample collection device1100 are not excluded. This de-coupling of the collection device and thewound creation device allows for the use of a more sophisticated,possible non-disposable wound creation device 1250 that can create amore controlled, reduced-pain wound creation experience.

FIG. 11W shows that the sample collection device 1100 can be aligned tobe more or less horizontal to be neutral with regards to gravity effectson the sample collection. Other mounting configurations of device 1100to would creation device 1250 are not excluded.

Referring now to FIGS. 11X to 11Z, still further embodiments of varioussample collection devices will now be described. FIG. 11X shows a samplecollection device 1240 where a shaped front end 1236 may be used withthe device 1240. This shaped front end 1236 is similar to thatpreviously described. A vacuum source 1270 can be used to assist indrawing bodily fluid sample into the device 1240. The vacuum source 1270may be linked to the body of device 1240 and/or to the shaped front end1236. It should be understood that any of the embodiments described inthis disclosure can be adapted for use with a sample acquisition assistdevice such as but not limited to a vacuum source 1270.

FIG. 11Y shows yet another embodiment of a sample collection device.This embodiment uses a pipette system having a tip 1280 for collectingsample fluid. The tip may include a coaxially mounted tissue penetratingmember 1282. Optionally, a side mount or angled tissue penetratingmember 1284 is shown to create the wound at the target site. The pipettesystem with tip 1280 can apply vacuum to pull sample fluid from thesubject. Optionally, a shaped front end 1236 may be used with the tip1280 to assist in skin stretching or tissue reshaping at the targetsite.

FIG. 11Z shows that some embodiments may use a diaphragm 1291 linkedactuation mechanism to create a vacuum for drawing blood sample. Thislinkage allows for the diaphragm to create a vacuum on the return strokeof the tissue penetrating member 1292 from the target site. In oneembodiment, the tissue penetrating members 1292 are microneedles. Theactuation of the tissue penetrating members as indicated by arrows 1294launches the tissue penetrating members 1292 and on the return path,creates the vacuum due to the motion of the diaphragm linked to themotion of the tissue penetrating member 1292. One or more vessels 1296can be coupled to hold fluid collected by the device 1290. Someembodiments may have only one vessel 1296. Some embodiments may have oneset of vessels 1296. Some embodiments may have multiple sets of vessels1296. Some embodiments may be mounted externally on device 1290. Someembodiments may be mounted internally in device 1290. There may bevariations and alternatives to the embodiments described herein and thatno single embodiment should be construed to encompass the entireinvention.

Vertical Outflow Restrictors

FIG. 11E also more clearly shows that there are sleeves 1156 around theadapter 1150 and 1152. Although only shown in FIGS. 11A-11F, it shouldbe understood that sleeves with or without vents may be configured foruse with any of the embodiments contemplated herein. As seen in theembodiment of FIG. 11E, the channels may be defined by needles. Thesesleeves 1156 prevent premature flow of fluid sample out from the adapterchannels 1150 and 1152 before the vessels 1146 a and 1146 b engage theneedles. Because of the low volumes of sample fluid being acquired,preventing premature flow reduces the amount of fluid loss associatedwith transfer of fluid from the channels to the vessels. In oneembodiment, the sleeves 1156 can minimize that fluid loss by providing asleeve that is liquid tight, but not air tight. If the sleeve wereairtight, it may prevent the capillary action of the channels fromworking properly. Optionally, some embodiments may locate vents near thebase of the needle, away from the tip, such that the sleeve can containthe sample at locations away from the vents.

FIG. 11F shows that in an exemplary embodiment, the sleeve 1156 isconfigured to have an opening 1158 through the sleeve. This provides animproved embodiment over traditional sleeves which are typically looselyfitted over a needle. Because of the loose fit, in traditional sleeves,there is sleeve space in the tip and in side wall space between theneedle and the sleeve within which fluid sample can accumulate. Althougha sleeve of this design can help prevent greater loss of fluid byrestricting the loss to a defined amount as compared to a needle withouta sleeve which can lose fluid continuously, the fluid accumulating inthe sleeve area along the tip and side wall is still lost and notcollected by the vessels 1146 a or 1146 b. The sleeve 1156 may alsoinclude a narrowed area 1176 to facilitate engagement of the sleeveagainst the device providing fluid communication with the channels 1126and 1128, such as but not limited to the needle, probe, tube, channel,or other adapter channel 1150.

In the embodiment of FIG. 11F, the opening 1158 is sized based oncalculations which are sufficient to withstand fluid pressure associatedwith the flow from the capillary action of the channels in sample fillportion 1120. This forces allows the opening 1158 to be there to ventair from the channel but also prevent fluid from exiting the sleeveuntil the vessels 1146 a and 1146 b are pushed to engage the adapterchannels 1150 and 1152. Because of the vent effect created by theopening 1158, the side wall and other areas of the sleeve can be made tomuch more tightly engage the needle than in traditional sleeves. Thisreduces the gap space between the needle and the sleeve and thusminimizes the amount of fluid that can be lost as compared to sleeveswithout a vent hole which have a much greater gap space due to thelooseness of the fit. Additionally, the opening 1158 can also be sizedsuch once fluid reaches the opening, that it provides enough resistanceso that flow out from the channel or needle is also stopped so that hereis minimal fluid loss in any gap between the sleeve and the needle tip.

The calculations for sizing the opening are as shown in FIG. 12. Thedesire is to balance the forces such that there is sufficientleak-prevention force associated with the hydrophobic material definingthe vent to contain outflow of sample fluid outside of the sleeve. InFIG. 12, the side walls of the sleeve 1156 may be in direct contact withthe needle or in some embodiments, there may be a gap along the sidewallwith the sleeve. In one embodiment, the sleeve 1156 comprises ahydrophobic material such as but not limited to thermoplastic elastomer(TPE), butyl rubber, silicone, or other hydrophobic material. In oneembodiment, the thickness of the sleeve will also determine the lengthof the side walls of the opening or vent 1158 in the sleeve 1156.

The opening 1158 may be located at one or more positions along thesleeve 1156. Some may have it as shown in FIG. 12. Alternatively, someembodiments may have the opening 1158 on a side wall of the sleeve.Other locations are not excluded. Optionally, the sleeve 1156 may havemultiple openings through the sleeve, but configured such that fluiddoes not exit from the sleeve and resistance from the openings issufficient to prevent additional outflow from the channel until thevessels 1146 a or 1146 b are engaged and in fluid communication with thechannels.

With regards to how the device 1100 is used to collect a sample, in onetechnique, the sample collection device 1100 is held to engage thetarget bodily fluid and is held in place until a desired fill level isreached. During this time, the device 1100 may be held horizontally tominimize gravitational force that would need to be overcome if thedevice 1100 were held more vertically. After a fill level is reached,the device 1100 may either be disengaged from the target fluid and thenvessels 1146 a and 1146 b engaged to draw collected fluid into thevessels. Optionally, the device 1100 may be left in contact with thetarget fluid and the vessels engaged into fluid contact with thechannels so that the fill will draw fluid in the channel and perhapsalso any additional sample fluid that remains at the target site. Thismay ensure that enough bodily fluid is drawn into the vessels.

After filling the vessels 1146 a and 1146 b, they may be prepared forshipment. Optionally, they may be sent for pre-treatment before beingshipped. Some embodiments of the vessels 1146 a and 1146 b include amaterial in the vessel of a density such that after a pre-treatment suchas centrifugation, the material due to its selected density willseparate one portion of the centrifuged sample from another portion ofthe centrifuged sample in the same vessel.

The vessel 1146 a or 1146 b may have a vacuum and/or negative pressuretherein. The sample may be drawn into the vessel when the channel isbrought into fluidic communication with the vacu-vessel. Optionally, thevessel may take the form of a test tube-like device in the nature ofthose marketed under the trademark “Vacutainer” by Becton-DickinsonCompany of East Rutherford, N.J. The device may remain in a compressedstate with the base 1140 closing gap 1154 while the sample is beingtransferred to the vessel. The sample may fill the entire vessel or aportion of the vessel. The entirety of the sample (and/or greater than90%, 95%, 97%, 98%, 99%, 99.5% or 99.9% of the sample) from the channelsmay be transferred to the vessels. Alternatively, only a portion of thesample from the channels may be transferred to the vessels.

In one embodiment as described herein, a two-stage filling of the samplefluid into the sample collection device 1100 allows for i) meteredcollection of the sample fluid to ensure that a sufficient amount isobtained in a collection channel that is treated to prevent prematureclotting and then ii) an efficient manner of transferring a highpercentage of the sample fluid into the vessel. This low loss filling ofvessel from pre-fill channels to meter a minimum amount of sample fluidinto the vessel 1146 provides for multiple advantages, particularly whendealing with collecting small volumes of sample fluid. Pre-filling thechannels to a desired level ensures sufficient volume is present in thevessel to perform the desired testing on the sample fluid.

As described herein, the entire device including the sample fill portion1120, support 1130, and base 1140 are entirely transparent ortranslucent to allow for visualization of the components therein.Optionally, only one of the sample fill portion 1120, support 1130, andbase 1140 are fully transparent or translucent. Optionally, only selectportions of sample fill portion 1120, support 1130, or base 1140 aretransparent or translucent. The user may then more accurately determinewhen to perform various procedures based on progression of sample fluidfilling and engagement of the sample vessels to the channels in samplefill portion 1120. Air bubbles in the collection channel may be visibleduring filling and if they are seen, a user may adjust the position ofthe sample collection device 1100 to better engage the target samplefluid to minimize air being drawn into the channels. It will also allowthe user to know when to breakaway or disengage pieces such as the baseor vessel holder 1140 when filling is completed.

It should be understood that other methods can be used to preventoutward sample flow from the adapter channels 1150 and 1152 if thedevice is held at a non-horizontal angle such as but not limited todownwardly in a vertical manner. In one embodiment, a frit 1194 can beused with needles with a central bore that are used as the adapterchannels 1150 and 1152. The frits can be in the body of samplecollection device or on the collection vessels. In some embodiments, thefrits comprise of a material such as but not limited to PTFE.Optionally, some embodiments may use tape/adhesive over the needles thatare functioning as the adapter channels 1150 and 1152. In oneembodiment, the tape and/or adhesive may be used to cover the needleopenings to prevent premature discharge of sample. Optionally, someembodiments may have adapter channels 1150 and 1152 having hydrophobicsurface to prevent controlled outflow from the adapter channel openingsleading toward the sample vessels. In some embodiments, the adapterchannels 1150 and 1152 are needles with hydrophobic material only on theinterior surfaces near an exit. Optionally, the hydrophobic material isonly on the exterior needle surfaces near an exit. Optionally, thehydrophobic material is on interior and exterior needle surfaces.Optionally, another method of preventing downward flow is increasing thesurface area of the capillaries by varying the cross-section. By way ofnon-limiting example, some embodiments may introduce teeth- orfinger-like structures within the capillary in order increase surfaceare in the cross-section of the capillary. Optionally, some embodimentsmay include fins oriented toward and/or against the fluid flow withinthe capillary in order increase surface are in the cross-section of thecapillary. There may be variations and alternatives to the embodimentsdescribed herein and that no single embodiment should be construed toencompass the entire invention.

One Sample Collector Location to Multiple Channels

Referring now to FIGS. 13A-13B, yet another embodiment as describedherein will now be described. FIG. 13A shows a top down view of a samplefill portion 1320 with a single collection location 1322 such as but notlimited to a collection well where two channels 1324 and 1326 meet todraw fluid away from the single collection location 1322. Optionally,some embodiments may use an Y-split channel configuration wherein only asingle channel lead away from the collection location 1322 and thensplits into channels 1324 and 1326 after having been a single commonchannel leading away from the collection location 1322. Membersproviding fluid communication to the channels 1324 and 1326, such as butnot limited to a needle, probe, tube, channel, hollow elongate member,or other structure, may be coupled to one end of the sample fill portion1320.

FIG. 13B shows a side-cross-sectional view, wherein the collectionlocation 1322 is shown and in fluidic communication with channel 1326which is in turn in fluid communication with an adapter channel 1352such as but not limited to a fluid communication member. Someembodiments, the fluid communication member may have sufficientstiffness and a sufficiently penetrating tip to pierce a septum, cap, orother structure of the vessel. Some may have the adapter channel 1352,1150, or the like to be a non-coring structure so as not to leave behinda hole that will not seal in the septum, cap, or other structure of thevessel.

As seen in FIG. 13B, sample fluid may be applied or dropped into thecollection location 1322 as indicated by droplet D. Optionally, some maydirectly apply or directly contact the collection location 1322 to applythe sample fluid. Although the embodiments herein are shown to use onlya single collection location 1322, it should be understood that otherembodiments where multiple channels couple to a common sample collectionpoint are envisioned. By way of nonlimiting example, one embodiment of acollection device may have two collection locations 1322, each with itsown set of channels leading away from its respective collectionlocation. Some embodiments may combine common collection point channelsshown in FIGS. 13A-B with channels that are separate such as shown inFIGS. 11A-11F. Other combinations of common collection locationstructure with other structures with separate channels are not excluded.

FIG. 13B also shows that this embodiment may include one or more tissuepenetrating members 1327 configured to extend outward from thecollection location 1322. In one embodiment, this enables the user toplace target tissue simultaneously over the collection location 1322 andthe wound creation location for fluid sample acquisition. Optionally, atrigger 1323 can be positioned to launch the tissue penetrating member.Optionally, the trigger is built into a tissue interface of the deviceto enable launch of the device when the target tissue is contactedand/or when sufficient pressure or contact is in place. This overlap ofthese two locations allows for simplified protocol for users to followfor successful sample acquisition. The tissue penetration member(s) 1327may be actuated by one or more actuation techniques such as but notlimited to spring actuated, spring/cam actuated, electronicallyactuated, or single or multiple combinations of the foregoing. It shouldbe understood that other assist methods such as but not limited tovacuum sources, tissue stretching devices, tissue engagement nosepieces, or the like may be used alone or in combination with any of theforegoing for improved sample acquisition.

Referring now to FIG. 13C, a still further embodiment of a samplecollection device will now be described. This embodiment shows acartridge 1400 with a sample collection device 1402 integrated therein.There is a collection location 1322 and one or more sample openings 1325and 1329 where sample collection at location 1322 can then be accessedsuch as but not limited to handling by a pipette tip (not shown). Thesample from droplet D will travel along pathway 1326 as indicated byarrow towards the openings 1325 and 1329, where the sample in theopening and any in the pathways 1324 and/or 1326 leading towards theirrespective openings 1325 and 1329 are drawn into the pipette P. Asindicated by arrows near the pipette P, the pipette P is movable in atleast one axis to enable transport of sample fluid to the desiredlocation(s). In this embodiment, the cartridge 1400 can have a pluralityof holding vessels 1410 for reagents, wash fluids, mixing area,incubation areas, or the like. Optionally, some embodiments of thecartridge 1400 may not include any holding vessels or optionally, onlyone or two types of holding vessels. Optionally, in some embodiments,the holding vessels may be pipette tips. Optionally, in someembodiments, the holding vessels are pipette tips that are treated tocontain reagent(s) on the tip surface (typically the interior tipsurface although other surfaces are not excluded). Optionally, someembodiments of the cartridge 1400 may include only the sample collectiondevice 1402 without the tissue penetrating member or vice versa.

Referring now to FIG. 13D, a side cross-sectional view of the embodimentof FIG. 13C is shown. Optionally, a tissue penetrating member 1327 maybe included for use with creating the wound for the sample fluid to becollected at location 1322.

FIG. 14 shows that the sample fill portion 1320 may be joined withsupport 1330 and 1340 to form the sample collection device 1300. Theremay be a visualization window 1312 to see if sample fluid has reached adesired fill level. A force-exerting component, such as a spring 1356 orelastic may be included. The channel holder may keep the channel affixedto the support. In one embodiment, the holder may prevent the channelfrom sliding relative to the support. It may use a press fit, mechanicalfastening, adhesive, or other attachment technique to couple to thechannel. The holder may optionally provide a support upon which aforce-exerting component, such as a spring, may rest.

In one example, the engagement assemblies may include a spring 1356which may exert a force so that the base 1340 is at an extended state,when the spring is at its natural state. When the base is at itsextended state, space may be provided between the vessels 1346 a, 1346 band the engagement assemblies. In some instances, when the base 1340 isin its extended state, the second ends of the channels may or may notcontact the caps of the vessels. The second ends of the fluidcommunication members 1352 may be in a position where they are not influid communication with the interiors of the vessels.

Bringing the support 1330 and the base 1340 together will bring thechannels 1324 and 1326 into fluid communication with the vessels 1346 aand 1346 b when the members 1352 penetrate through the cap on thevessels and thus draw sample fluid into the vessels 1346 a and 1346 b.

The vessel 1346 a or 1346 b may have a vacuum and/or negative pressuretherein. The sample may be drawn into the vessel when the channel isbrought into fluidic communication with the vacu-vessel. The device mayremain in a compressed state with the base 1340 positioned so thatvessels are in fluid communication with the channels 1326 and 1328 whenthe sample fluid is being transferred to the vessels. The sample mayfill the entire vessel or a portion of the vessel. The entirety of thesample (and/or greater than 90%, 95%, 97%, 98%, 99%, 99.5% or 99.9% ofthe sample) from the channels may be transferred to the vessels.Alternatively, only a portion of the sample from the channels may betransferred to the vessels.

As seen in FIG. 15, in one embodiment as described herein, a two-stagefilling of the sample fluid into the sample collection device 1300allows for i) metered collection of the sample fluid to ensure that asufficient amount is obtained in a collection channel that is treated toprevent premature clotting and then ii) an efficient manner oftransferring a high percentage of the sample fluid into the vessel. Thislow loss filling of vessel from pre-fill channels to meter a minimumamount of sample fluid into the vessel 1346 provides for multipleadvantages, particularly when dealing with collecting small volumes ofsample fluid. Pre-filling the channels to a desired level ensuressufficient volume is present in the vessel to perform the desiredtesting on the sample fluid.

Referring now to FIGS. 16 and 17, still further embodiments will now bedescribed. FIG. 16 shows a blood collection device 1300 with a secondarycollection area 1324 around the collection location 1322. The secondarycollection area 1324 can be used to direct any overflow, spilled, ormis-directed fluid sample towards the collection location 1322.

FIG. 17 further shows that the vessels 1346 a and 1346 b may each havean identifier associated with the vessels 1346 a and 1346 b. FIG. 17shows that in one nonlimiting example, the identifier 1600 and 1602 maybe at least one of: a barcode (e.g., 1-D, 2-D, or 3-D), quick response(QR) code, image, shape, word, number, alphanumeric string, color, orany combination thereof, or any type of visual identifier. Others mayuse identifiers that are not in the visible spectrum. Others may useRFID tags, RF identifiers, IR emitting tags, or other markers that donot rely on identification through signals sent through the visualspectrum.

Identifiers 1600 and 1602 may be used to identify sample and/or types ofsample in a sample collection device. There may be one or moreidentifiers per vessel. Some may also use identifiers on the vesselholders. Identifiers may identity the sample collection device, one ormore individual vessels within the device, or components of the device.In some instances, the sample collection device, a portion of the samplecollection device, and/or the vessels may be transported. In oneexample, the sample collection device, portion of the sample collectiondevice may be transported via a delivery service, or any other servicedescribed elsewhere herein. The sample may be delivered to perform oneor more test on the sample.

The sample identity and/or the identity of the individual who providedthe sample could be tracked. Information associated with the individualor individuals (e.g., name, contact information, social security number,birth date, insurance information, billing information, medical history)and other information of who provided the sample may be included. Insome instances, the type of sample (e.g., whole blood, plasma, urine,etc.) may be tracked. The types of reagents that the sample will haveencountered (e.g., anticoagulants, labels, etc.) could also be tracked.Additional information about the sample collection, such as date and/ortime of collection, circumstances under which sample was collected,types of tests to be run on the sample, insurance information, medicalrecords information, or any other type of information may be considered.

Identifiers may assist with tracking such information. The identifiersmay be associated with such information. Such information may be storedoff-board the sample collection device, on-board the sample collectiondevice, or any combination thereof. In some instances, the informationmay be stored on one or more external devices, such as servers,computers, databases, or any other device having a memory. In someinstances, the information may be stored on a cloud computinginfrastructure. One or more resources that store the information may bedistributed over the cloud. In some instances, a peer-to-peerinfrastructure may be provided. The information may be stored in theidentifier itself, or may be associated with the identifier elsewhere,or any combination thereof.

An identifier may provide unique identification, or may provide a highlikelihood of providing unique identification. In some instances, theidentifier may have a visible component. The identifier may be opticallydetectable. In some instances, the identifier may be discernible usingvisible light. In some examples, the identifier may be a barcode (e.g.,1-D, 2-D, or 3-D), quick response (QR) code, image, shape, word, number,alphanumeric string, color, or any combination thereof, or any type ofvisual identifier.

In other embodiments, the identifier may be optically detectable via anyother sort of radiation. For example, the identifier may be detectablevia infrared, ultraviolet, or any other type of wavelength of theelectromagnetic spectrum. The identifier may utilize luminescence, suchas fluorescence, chemiluminescence, bioluminescence, or any other typeof optical emission. In some instances, the identifier may be a radiotransmitter and/or receiver. The identifier may be a radiofrequencyidentification (RFID) tag. The identifier may be any type of wirelesstransmitter and/or receiver. The identifier may send one or moreelectrical signal. In some instances, GPS or other location-relatedsignals may be utilized with the identifier.

An identifier may include an audio component, or acoustic component. Theidentifier may emit a sound that may be discernible to uniquely identifythe identified component.

The identifier may be detectable via an optical detection device. Forexample, a bar code scanner may be capable of reading the identifier. Inanother example, a camera (e.g., for still or video images) or otherimage capture device may be capable of capturing an image of theidentifier and analyzing the image to determine the identification.

FIGS. 16 and 17 show examples of identifiers provided for use with asample collection device 1300 in accordance with an embodiment describedherein. In one example, a sample collection device may include a base1340 which may support and/or contain one or more vessels 1346 a, 1346b. Sample may be provided to the sample collection device. The samplemay be provided to the sample collection device via an inlet 1322. Thesample may travel to one or more vessels 1346 a, 1346 b within thedevice.

One or more identifier 1600, 1602 may be provided on the samplecollection device. In some embodiments, identifiers may be positioned ona base 1340 of the sample collection device. The identifiers may bepositioned on a bottom surface of the base, side surface of the base, orany other portion of the base. In one example, the base may have a flatbottom surface. The identifiers may be on the flat bottom surface of thebase. One or more indentation may be provided in the base. Theidentifier may be located within the indentation. The indentations maybe on the bottom or side surface of the base. In some embodiments, thebase may include one or more protrusion. The identifier may be locatedon the protrusion. In some instances, the identifiers may be provided onan exterior surface of the base. The identifiers may alternatively bepositioned on an interior surface of the base. The identifiers may bedetected from outside the sample collection device.

In some embodiments, the identifiers may be provided on the vessels 1346a, 1346 b. The identifiers may be on an exterior surface of the vesselsor an interior surface of the vessels. The identifiers may be detectablefrom outside the vessels. In some embodiments, the identifiers may beprovided on a bottom surface of the vessels.

In one example, the base may include an optically transmissive portion.The optically transmissive portion may be on a bottom of the base or aside of the base. For example, a transparent or translucent window maybe provided. In another example, the optically transmissive portion maybe a hole without requiring a window. The optically transmissive portionmay permit a portion inside the base to be visible. The identifiers maybe provided on an exterior surface of the base on the opticallytransmissive portion, an interior surface of the base but may be visiblethrough the optically transmissive portion, or on an exterior orinterior surface of the vessel but may be visible through the opticallytransmissive portion. In some instances, the identifier may be providedon an interior surface of the vessel, but the vessel may be opticallytransmissive so that the identifier is viewable through the vesseland/or optically transmissive portion.

The identifier may be a QR code or other optical identifier that may beoptically visible from outside the sample collection device. A QR codemay be visible through an optical window or hole at the bottom of thebase of the sample collection device. The QR code may be provided on thesample collection device base or on a portion of the vessel visiblethrough the base. An image capturing device, such as a camera or scannermay be provided externally to the sample collection device, and may becapable of reading the QR code.

A single or a plurality of QR codes or other identifiers may be providedon a sample collection device. In some instances, each vessel may haveat least one identifier, such as a QR code associated with it. In oneexample, at least one window may be provided in a base per vessel, andeach window may permit a user to view a QR code or other identifier. Forexample, two vessels 1346 a, 1346 b may be housed within a base 1340,each of which has an associated identifier 1600, 1602 discernible fromoutside the sample collection device.

The base 1340 may be separable from the support 1330 or other portionsof the sample collection device. The identifier(s) may be separated fromthe rest of the sample collection device along with the base.

In some embodiments, the identifiers may be provided with vessels housedby the base. Separating the base from the rest of the sample collectiondevice may cause the vessels to be separated from the rest of the samplecollection device. The vessels may remain within the base or may beremoved from the base. The identifiers may remain with the vessels evenif they are removed from the base. Alternatively, the identifiers mayremain with the base even if vessels are removed. In some instances,both the base and vessels may have identifiers so that the vessels andbases may be individually tracked and/or matched even when separated.

In some instances, any number of vessels may be provided within thesample collection device. The sample vessels may be capable of receivingsample received from a subject. Each sample vessel may have a uniqueidentifier. The unique identifier may be associated with any informationrelating to the sample, subject, device, or component of the device.

In some instances, each identifier for each vessel may be unique. Inother embodiments, the identifier on the vessel need not be unique, butmay be unique for the device, for the subject, or for the type ofsample.

A sample collection device may receive a sample from a subject. Thesubject may directly contact the sample collection device or provide thesample to the device. The sample may travel through the device to one ormore vessels within the device. In some instances, the sample may betreated prior to reaching the vessels. One or more coating or substancemay be provided within a sample collection unit and/or channel that mayconvey the sample to the vessels. Alternatively, no treatment isprovided to the sample prior to reaching the vessel. In someembodiments, the sample may or may not be treated within the vessel. Insome instances, a plurality of different types of treatments may beprovided to a sample before or when the sample reaches the vessel. Thetreatments may be provided in a preselected order. For example, a firsttreatment desired first, and may be provided upstream of a secondtreatment. In some instances, the sample is not treated at any point.

In some embodiments, the sample may be a blood sample. A first vesselmay receive whole blood and a second vessel may receive blood plasma.Anticoagulants may be provided along the fluid path and/or in thevessels.

Once the sample has been provided to the vessels and the vessels havebeen sealed, the vessels may be sent to a separate location for sampleanalysis. The separate location may be a laboratory. The separatelocation may be a remote facility relative to the sample collectionsite. The entire sample collection device may be sent to the separatelocation. One or more identifiers may be provided on the samplecollection device and may be useful for identifying the samplecollection device and/or vessels therein. Alternatively, the base 1340may be removed from the sample collection device and may be sent to theseparate location with the vessels therein. One or more identifiers maybe provided on the base and may be useful for identifying the baseand/or vessels therein. In some instances, vessels may be removed fromthe base and may be sent to the separate location. One or moreidentifier may be provided on each vessel, and may be useful foridentifying the vessels.

The identifiers may be read by any suitable technique. By way of exampleand not limitation, in some instances, the identifiers are read using anoptical detector, such as an image capture device or barcode scanner. Inone example, an image capture device may capture an image of a QR code.Information relating to the vessel may be tracked. For example, when avessel arrives at a location, the identifier may be scanned, and recordof the arrival of the vessel may be kept. The progress and/or locationof the vessel may be updated actively and/or passively. In someinstances, the identifier may need to be scanned intentionally in orderto determine the location of the vessel. In other examples, theidentifier may actively emit a signal that may be picked up by signalreaders. For example, as an identifier travels through a building,signal readers may track the location of the identifier.

In some instances, reading the identifier may permit a user to accessadditional information associated with the identifier. For example, theuser may capture an image of the identifier using a device. The deviceor another device may display information about the sample, subject,device, component of the device, or any other information describedelsewhere herein. Information about tests to be conducted and/or testresults may be included. The user may perform subsequent tests oractions with the sample based on information associated with theidentifier. For example, the user may direct the vessel to theappropriate location for a test. In some instances, the vessel may bedirected to an appropriate location and/or have appropriate sampleprocessing (e.g., sample prep, assay, detection, analysis) performed onthe contents of the vessel in an automated fashion without requiringhuman intervention.

Information relating to sample processing may be collected andassociated with the identifier. For example, if a vessel has anidentifier and sample processing has been performed on the contents ofthe vessel, one or more signals produced in response to the sampleprocessing may be stored and/or associated with the identifier. Suchupdates may be made in an automated fashion without requiring humanintervention. Alternatively, a user may initiate the storing ofinformation or may manually enter information. Thus, medical recordsrelating to a subject may be aggregated in an automated fashion. Theidentifiers may be useful for indexing and/or accessing informationrelated to the subject.

Sample Vessels

FIGS. 18A-18B show one nonlimiting example of a sample vessel 1800 thatmay be utilized with a sample collection device in accordance with anembodiment described herein. In some instances, the sample vessels maybe supported by the sample collection device. Optionally, the samplevessels may be encompassed or surrounded by a portion of the samplecollection device. In one example, the sample collection device may havea first configuration where the sample vessels are completely enclosed.A second configuration may be provided where the sample collectiondevice may be opened and at least a portion of the sample vessels may beexposed. In some examples, the sample vessels may be supported and/or atleast partially enclosed by a holder of the sample collection device.The holder may be separable from the rest of the sample collectiondevice, thereby providing access to the sample vessels therein.

In the case of bodily fluid collection, the sample fluid may beextracted from the patient using a sample collection device such as butnot limited to that described in U.S. Patent Application Ser. No.61/697,797 filed Sep. 6, 2012 and U.S. Patent Application Ser. No.61/798,873 filed Mar. 15, 2013, both of which are fully incorporatedherein by reference for all purposes. In the non-limiting example ofblood samples, some embodiments may collect the blood sample throughcollection of capillary blood from the subject. This may occur by way ofa wound, a penetration site, or other access site to capillary bloodfrom the subject. Optionally, blood could also be collected byvenipuncture or other puncture of a blood vessel to obtain blood samplefor loading into the sample vessel(s). For example, the blood could becollected by a device configured for collection of a small volume ofblood by venipuncture. Such a device, for example, may include a hollowneedle fluidically connected with or capable of being fluidicallyconnected with a vessel having a small interior volume. The vesselhaving a small interior volume may have an interior volume, for example,of equal to or no more than 5 ml 4 ml, 3 ml, 2 ml, 1 ml, 750 μl, 500 μl,400 μl, 300 μl, 200 μl, 100 μl, 90 μl, 80 μl, 70 μl, 60 μl, 50 μl, 40μl, 30 μl, 20 μl, 10 μl, or 5 μl. Other types of devices and techniquesused to collect bodily fluid are not excluded.

A bodily fluid may be drawn from a subject and provided to a device in avariety of ways, including but not limited to, fingerstick, lancing,injection, pumping, swabbing, pipetting, venous draw, venipuncture,and/or any other technique described elsewhere herein. In someembodiments, the sample may be collected from the subject's breath. Thebodily fluid may be provided using a bodily fluid collector. A bodilyfluid collector may include a lancet, capillary, tube, pipette, syringe,needle, microneedle, pump, or any other collector described elsewhereherein. In some embodiments, the sample may be a tissue sample which maybe provided from the subject. The sample may be removed from the subjector may have been cast off by the subject.

In one embodiment, a lancet punctures the skin of a subject andwithdraws a sample using, for example, gravity, capillary action,aspiration, pressure differential or vacuum force. The lancet, or anyother bodily fluid collector, may be part of the device, part of acartridge of the device, part of a system, or a standalone component.Where needed, the lancet or any other bodily fluid collector may beactivated by a variety of mechanical, electrical, electromechanical, orany other known activation mechanism or any combination of such methods.

In one example, a subject's finger (or other portion of the subject'sbody) may be punctured to yield a bodily fluid. The bodily fluid may becollected using a capillary tube, pipette, swab, drop, or any othermechanism known in the art. The capillary tube or pipette may beseparate from the device and/or a cartridge of the device that may beinserted within or attached to a device, or may be a part of a deviceand/or cartridge. In another embodiment where no active mechanism isrequired, a subject can simply provide a bodily fluid to the deviceand/or cartridge, as for example, with a saliva sample.

A bodily fluid may be drawn from a subject and provided to a device in avariety of ways, including but not limited to, fingerstick, lancing,injection, and/or pipetting. The bodily fluid may be collected usingvenous or non-venous methods. The bodily fluid may be provided using abodily fluid collector. A bodily fluid collector may include a lancet,capillary, tube, pipette, syringe, venous draw, or any other collectordescribed elsewhere herein. In one embodiment, a lancet punctures theskin and withdraws a sample using, for example, gravity, capillaryaction, aspiration, or vacuum force. The lancet may be part of thedevice, part of the cartridge of the device, part of a system, or astandalone component. Where needed, the lancet may be activated by avariety of mechanical, electrical, electromechanical, or any other knownactivation mechanism or any combination of such methods. In one example,a subject's finger (or other portion of the subject's body) may bepunctured to yield a bodily fluid. Examples of other portions of thesubject's body may include, but are not limited to, the subject's hand,wrist, arm, torso, leg, foot, or neck. The bodily fluid may be collectedusing a capillary tube, pipette, or any other mechanism known in theart. The capillary tube or pipette may be separate from the deviceand/or cartridge, or may be a part of a device and/or cartridge. Inanother embodiment where no active mechanism is required, a subject cansimply provide a bodily fluid to the device and/or cartridge, as forexample, could occur with a saliva sample. The collected fluid can beplaced within the device. A bodily fluid collector may be attached tothe device, removably attachable to the device, or may be providedseparately from the device.

Sample obtained from a subject may be stored in a sample vessel 1800. Inone embodiment described herein, the sample vessel 1800 comprises a body1810 and a cap 1820. In some instances, at least portions of the samplevessel body may be formed from a transparent or translucent material.The sample vessel body may permit a sample provided within the samplevessel body to be visible when viewed from outside the sample vessel.The sample vessel body may be optically transmissive. The sample vesselbody may be formed of a material that may permit electromagneticradiation to pass through. In some instances, the sample vessel body maybe formed of a material that may permit selected wavelengths ofelectromagnetic radiation to pass through while not permitting othernon-selected wavelengths of electromagnetic radiation to pass through.In some instances a portion or all of the body may be formed of amaterial that is opaque along selected wavelengths of electromagneticradiation, such as wavelengths for visible light. Optionally, someportions of the sample vessel body may be shaped to provide a certainoptical path length. Optionally, some portions of the sample vessel bodymay be shaped to provide a flat surface (exterior and/or interior) orother structure to allow for analysis of sample while it is in thesample vessel.

In one embodiment, an open end and a closed end may be provided on asample vessel body 1810. The open end may be a top end 1812 of thesample vessel 1800, which may be at the end which may be configured toengage with a cap. The closed end may be a bottom end 1814 of the samplevessel, which may be at the end of the sample vessel opposite the cap.In alternative embodiments, a bottom end may also be an open end thatmay be closable with a floor. In some embodiments, the cross-sectionalarea and/or shape of the top end and the bottom end may be substantiallythe same. Alternatively, the cross-sectional area of the top end may belarger than the cross-sectional area of the bottom end, or vice versa.There may be variations and alternatives to the embodiments describedherein and that no single embodiment should be construed to encompassthe entire invention.

In one embodiment, a sample vessel body may have an interior surface andan exterior surface. The surfaces of the sample vessel body may besmooth, rough, textured, faceted, shiny, dull, contain grooves, containridges, or have any other feature. The surface of the sample vessel bodymay be treated to provide a desired optical property. The interiorsurfaces and exterior surfaces may have the same properties or may bedifferent. For example, an exterior surface may be smooth while theinterior surface is rough.

Optionally, the sample vessel body may have a tubular shape. In someinstances, the sample vessel body may have a cylindrical portion. Insome instances, the sample vessel may have a circular cross-sectionalshape. Alternatively, the sample vessel may have any othercross-sectional shape which may include elliptical, triangular,quadrilateral (e.g., square, rectangular, trapezoidal, parallelogram),pentagonal, hexagonal, heptagonal, octagonal, or any other shape. Thecross-sectional shape of the sample vessel may or may not have a convexand/or concave shape. The cross-sectional shape of the sample vessel mayremain the same along the length of the sample vessel, or may vary. Thesample vessel may have a prismatic shape along the length of the body.The prism may have a cross-sectional shape as those described herein.

Optionally, the bottom 1814 of the sample vessel may be flat, tapered,rounded, or any combination thereof. In some instances, the samplevessel may have a hemispherical bottom. In other embodiments, the samplevessel may have a rounded bottom with a flat portion. The sample vesselmay or may not be capable of standing on a flat surface on its own.

In one embodiment, the sample vessels 1800 may be sized to contain asmall fluid sample. In some embodiments, the sample vessels may beconfigured to contain no more than about 5 ml, 4 ml, 3 ml, 2 ml, 1.5 mL,1 mL, 900 μL, 800 μL, 700 μL, 600 μL, 500 μL, 400 μL, 300 μL, 250 μL,200 μL, 150 μL, 100 μL, 80 μL, 50 μL, 30 μL, 25 μL, 20 μL, 10 μL, 7 μL,5 μL, 3 μL, 2 μL, 1 μL, 750 nL, 500 nL, 250 nL, 200 nL, 150 nL, 100 nL,50 nL, 10 nL, 5 nL, 1 nL, 500 pL, 300 pL, 100 pL, 50 pL, 10 pL, 5 pL, or1 pL. By way of non-limiting example, the sample vessels may have theinformation storage units thereon such as discussed for FIGS. 1F and 1G.In one non-limiting example, the sample vessels 100 may hold the smallvolume of sample fluid in liquid form without the use of a wickingmaterial, mesh, solid matrix, or the like to hold the sample fluidduring transport. This allows the sample fluid to be substantiallyremoved in liquid form from the sample vessel without loss of sample orsample integrity due to liquid being absorbed by the wicking or othermaterial.

Optionally, the sample vessels 1800 may be configured to contain no morethan several drops of blood, a drop of blood, or no more than a portionof a drop of blood. For example, the sample vessel may have an interiorvolume of no greater than the amount of fluid sample it is configured tocontain. Having a small volume sample vessel may advantageously permitstorage and/or transport of a large number of sample vessels within asmall volume. This may reduce resources used to store and/or transportthe sample vessels. For example, less storage space may be required.Additionally, less cost and/or fuel may be used to transport the samplevessels. For the same amount of exertion, a larger number of samplevessels may be transported.

In some embodiments, the sample vessel 1800 may have a small length. Forexample, the sample vessel length may be no greater than 8 cm, 7 cm, 6cm, 5 cm, 4 cm, 3.5 cm, 3 cm, 2.5 cm, 2 cm, 1.7 cm, 1.5 cm, 1.3 cm, 1.1cm, 1 cm, 0.9 cm, 0.8 cm, 0.7 cm, 0.6 cm, 0.5 cm, 0.4 cm, 0.3 cm, 0.2cm, 0.1 cm, 700 um, 500 m, 300 um, 100 um, 70 um, 50 um, 30 um, 10 um, 7um, 5 um, 30 um, or 1 um. In some instances, the greatest dimension ofthe sample vessel (e.g., length, width, or diameter) may be no greaterthan 8 cm, 7 cm, 6 cm, 5 cm, 4 cm, 3.5 cm, 3 cm, 2.5 cm, 2 cm, 1.7 cm,1.5 cm, 1.3 cm, 1.1 cm, 1 cm, 0.9 cm, 0.8 cm, 0.7 cm, 0.6 cm, 0.5 cm,0.4 cm, 0.3 cm, 0.2 cm, 0.1 cm, 700 um, 500 m, 300 um, 100 um, 70 um, 50um, 30 um, 10 um, 7 um, 5 um, 30 um, or 1 um.

The sample vessel 1800 may have any cross-sectional area. Thecross-sectional area may be no greater than about 16 cm², 8 cm², 7 cm²,6 cm², 5 cm², 4 cm², 3.5 cm², 3 cm², 2.5 cm², 2 cm², 1.5 cm², 1 cm², 0.9cm², 0.8 cm², 0.7 cm², 0.6 cm², 0.5 cm², 0.4 cm², 0.3 cm², 0.2 cm², 0.1cm², 0.07 cm², 0.05 cm², 0.03 cm², 0.02 cm², 0.01 cm², 0.5 cm², 0.3 cm²,or 0.1 cm². The cross-sectional area may remain the same or may varyalong the length of the sample vessel.

The sample vessel 1800 may have any thickness. The thickness may remainthe same along the length of the sample vessel or may vary. In someinstances, the thickness may be selected and/or may vary in order toprovide a desired optical property. In some instances, the thickness maybe no greater than 5 mm, 3 mm, 2 mm, 1 mm, 700 um, 500 um, 300 um, 200um, 150 um, 100 um, 70 um, 50 um, 30 um, 10 um, 7 um, 5 um, 3 um, 1 um,700 nm, 500 nm, 300 nm or 100 nm.

In one embodiment, the sample vessel 1800 may have a shape conducive toenabling centrifugation of small volume blood samples. This allows thecollected sample in the sample vessels to be taken directly to acentrifuge without having to further transfer the sample fluid to yetanother sample vessel that is used in the centrifuge device.

Optionally, the sample vessels may contain a cap 1820. The cap 1820 maybe configured to fit over an open end of the sample vessel. The cap mayblock the open end of the sample vessel. The cap may fluidically sealthe sample vessel. The cap may form a fluid-tight seal with the samplevessel body. For example, the cap may be gas and/or liquid impermeable.Alternatively, the cap may permit certain gases and/or liquids to passthrough. In some instances, the cap may be gas permeable while beingliquid impermeable. The cap may be impermeable to the sample. Forexample, the cap may be impermeable to whole blood, serum or plasma.

Optionally, the cap may be configured to engage with the sample vesselbody in any manner. For example, the cap may be press-fit with thesample vessel body. A friction fit and/or interference fit may permitthe cap to stay on the body. In other examples, a locking mechanism maybe provided, such as a sliding mechanism, clamp, fastener, or othertechnique. In some instances, the cap and/or the sample vessel body maybe threaded to permit a screw-type engagement. In other examples,adhesives, welding, soldering, or brazing may be utilized to connect thecap to the sample vessel body. The cap may be removably attached to thesample vessel body. Alternatively, the cap may be permanently affixed tothe sample vessel body.

In some instances, a portion of the cap may fit into a portion of thesample vessel body. The cap may form a stopper with the sample vesselbody. In some instances, a portion of the sample vessel body may fitinto a portion of the cap. The plug may include a lip or shelf that mayhang over a portion of the sample vessel body. The lip or shelf mayprevent the cap from sliding into the sample vessel body. In someinstances, a portion of a cap may overlie a top and/or side of thesample vessel body. Optionally, some embodiments may include anadditional part in the vessel assembly such as cap holder. In oneembodiment, the purpose of the cap holder is to maintain a tight sealbetween the cap and sample vessel. In one embodiment, the cap holderengages an attachment, lip, indentation, or other attachment location onthe outside of the sample vessel to hold the cap in position.Optionally, some embodiments can combine the function of both the capand the cap holder into one component.

In some embodiments, the sample vessel body may be formed of a rigidmaterial. For example, the sample vessel body may be formed of apolymer, such as polypropylene, polystyrene, or acrylic. In alternateembodiments, the sample vessel body may be semi-rigid or flexible. Thesample vessel body may be formed from a single integral piece.Alternatively, multiple pieces may be used. The multiple pieces may beformed from the same material or from different materials.

Optionally, the sample vessel cap may be formed of an elastomericmaterial, or any other material described elsewhere herein. In someinstances, the cap may be formed from a rubber, polymer, or any othermaterial that may be flexible and/or compressible. Alternatively, thecap may be semi-rigid or rigid. The sample vessel cap may be formed froma high friction material. The sample vessel cap may be capable of beingfriction-fit to engage with the sample vessel body. When the samplevessel cap is engaged with the sample vessel body, a fluid-tight sealmay be formed. The interior of the sample vessel body may be fluidicallyisolated from the ambient air. In some instances, at least one of thecap and/or portion of the sample vessel body contacting the cap may beformed from a high friction and/or compressible material.

In one embodiment, the cap 1820 may be a needle and/or acannula-penetrable self-sealing gas-proof closure in sealing engagementin the open end of the sample vessel so as to maintain a vacuum and/or aclose atmosphere inside the sample vessel. In some embodiments, theinterior of the sample vessel is only at a partial vacuum and not at afull vacuum. Excessive vacuum can damage formed blood components in thesample fluid. By way of non-limiting example, the partial vacuum is inthe range of about 50 to 60% of a full vacuum. Optionally, the partialvacuum does not exceed about 60% of a full vacuum. Optionally, thepartial vacuum does not exceed about 50% of a full vacuum. Optionally,the partial vacuum does not exceed about 40% of a full vacuum. By way ofnon-limiting example, the partial vacuum is in the range of about 10% toabout 90% of a full vacuum, or between about 20% to about 70%, orbetween about 30% to about 60% of a full vacuum. By way of non-limitingexample, the partial vacuum is in the range of about 10% to about 60% ofa full vacuum, or between about 20% to about 50%, or between about 30%to about 50% of a full vacuum. In this manner, a reduced amount of forceis exerted on the bodily fluid sample to minimize issues with regards tosample integrity. Optionally, after sample transfer, the atmosphere isat ambient pressure. Optionally, after sample transfer, the atmosphereis at some partial vacuum. Optionally, only one of the plurality ofsample vessels is at partial vacuum, while others are at higher vacuumlevels or at full vacuum.

In some embodiments, the cap 1820 may be a closure device having one endinterior of the sample vessel and another end exterior of the samplevessel, wherein the end interior having a surface in continuous sealingcontact with the sample vessel, the end interior having an annularsleeve extending from the surface toward the closed end, the annularsleeve having a first notch extending through a wall of the annularsleeve and juxtaposed against the sample vessel. In one embodiment, theclosure has an indented ring formed about the first notch of the endinterior and the indented ring engaging a hump of the tubular samplevessel.

Optionally, the sample vessel cap may be formed from a single integralpiece. Alternatively, multiple pieces may be used. The multiple piecesmay be formed from the same material or from different materials. Thecap material may be the same as or different from the sample vessel bodymaterial. In one example, the sample vessel body may be formed from anoptically transmissive material while the cap is formed from an opaquematerial.

Optionally, the cap 1820 may be removably engaged with the body. Aportion of the cap may be insertable into the body. The cap may includea lip which may rest on top of the body. The lip is not inserted intothe body. In this non-limiting example, the lip may prevent the cap frombeing entirely inserted into the body. The lip may form a continuousflange around the cap. In some instances, a portion of the lip mayoverlap or overlie a portion of the body. A portion of the body may beinsertable into a portion of the cap.

Optionally, the portion of the cap that may be insertable into the bodymay have a rounded bottom. Alternatively, the portion may be flat,tapered, curved, contoured, or have any other shape. The cap may beshaped to be easily insertable into the body.

In some instances, a depression may be provided at the top of the cap.The depression may follow the portion of the cap that is inserted intothe body. In some instances, a hollow or depression may be provided inthe cap. The depression may be capable of accepting a portion of achannel that may be used to deliver a sample to the sample vessel. Thedepression may assist with guiding the channel to a desired portion ofthe cap. In one example, the channel may be positioned within thedepression prior to bringing the channel and interior of the samplevessel into fluid communication.

Optionally, the channel and cap may be pressed together so that thechannel penetrates the cap and enters the interior of the sample vessel,thereby bringing the channel and interior of the sample vessel intofluid communication. In some instances, the cap may have a slit throughwhich the channel passes. Alternatively, the channel may poke throughuninterrupted cap material. The channel may be withdrawn from the samplevessel, thereby bringing the channel and sample vessel out of fluidcommunication. The cap may be capable of resealing when the channel isremoved. For the example, the cap may be formed of a self-healingmaterial. In some instances, the cap may have a slit that may close upwhen the channel is removed, thereby forming a fluid tight seal.

In some embodiments, the body may include one or more flange or othersurface feature. Examples of surface features may include flanges,bumps, protrusions, grooves, ridges, threads, holes, facets, or anyother surface feature. The flange and/or other surface feature maycircumscribe the body. The flange and/or surface feature may be locatedat or near the top of the body. The flange and/or other surface featuremay be located at the top half, top third, top quarter, top fifth, topsixth, top eighth, or top tenth of the body. The surface features may beuseful for support of the sample vessel within a sample collectiondevice. The surface features may be useful for removing the samplevessel from the sample collection device and/or positioning the samplevessel within the sample collection device. The flange and/or othersurface feature may or may not engage with the cap.

Optionally, the cap may have any dimension relative to the sample vesselbody. In some instances, the cap and/or body may have similarcross-sectional areas. The cap may have the same or a substantiallysimilar cross-sectional area and/or shape as the top of the body. Insome instances, the cap may have a lesser length than the body. Forexample, the cap may have a length that may be less than 60%, 50%, 40%,30%, 25%, 20%, 15%, 10%, 7%, 5%, 3% or 1% of the length of the body.

Referring now to FIGS. 18C to 18E, a still further embodiment of samplevessel 1800 may include a cap holder 1830 that fits over the cap to holdthe cap in place. By way of non-limiting example, the cap holder 1830may also include an opening in the cap holder 1830 that allows for amember such as an adapter to slide through and penetrate the cap 1820.FIG. 18C shows the parts in an exploded view.

FIG. 18D shows a cross-section view showing one embodiment wherein thesample vessel body 1810 having a cap 1820 covered by a cap holder 1830.As seen in FIG. 18D, the cap holder 1830 has a locking feature 1832 forsecuring the cap holder 1830 to the sample vessel body 1810 and/or thecap 1820. In one embodiment, the locking feature 1832 comprises aninterior ridge which will engage one or more of the ridges 1812 and 1814on the sample vessel body 1810. FIG. 18E shows a side view of the capholder 1830 coupled to the sample vessel body 1810.

In some instances, a surface (interior and/or exterior) of the samplevessel may be coated and/or treated with a material. For example, aninterior surface of the sample vessel may be coated with fixatives,antibodies, optical coatings, anticoagulant, sample additives and/orpreservatives. These may be the same or different from any materialcoatings in the channels. In one non-limiting example, the coating maybe but are not limited to polytetrafluoroethylene, poly-xylene,polysorbate surfactant (e.g. polysorbate 20) or other material as atreatment for surfaces to reduce the surface tension.

In embodiments, sample vessels may contain a blood clotting activator(e.g. thrombin, silica particles, glass particles), an antiglycolyticagent (e.g. sodium floride), or a gel to facilitate the separation ofblood cells from plasma. In examples, sample vessels may contain sodiumpolyanethol sulfonate (SPS), acid citrate dextrose additives, perchloricacid, or sodium citrate. Some embodiments may include at least onematerial from each of the above groupings. Optionally, it should also beunderstood that other additives or materials are not excluded,particularly if the additives do not interfere with each other in termsof functionality.

Optionally, the coating is applied on all interior surfaces of thesample vessel. Optionally, some embodiments may apply the coating in apattern covering only select areas in the sample vessel. Someembodiments may only cover upper interior regions of the sample vessel.Optionally, some may cover only lower interior regions of the samplevessel. Optionally, some may cover strips, lanes, or other geometricpatterns of the interior regions of the sample vessel. Optionally, someembodiments may also coat the surfaces of the cap, plug, or cover thatis used with the sample vessel. Some embodiments may have the surfaceswhere sample enters the sample vessel to be coated to provide for asmooth transfer of sample away from the entry area and towards adestination site such as but not limited to a bottom portion of thevessel.

Optionally, the coating may be a wet or dry coating. Some embodimentsmay have at least one dry coating and at least one wet coating. In someinstances one or more reagents may be coated and dried on the interiorsurface of the sample vessel. The coating may alternatively be providedin a moist environment or may be a gel. Some embodiments may include aseparator gel in the sample vessel to keep select portions of the sampleaway from other portions of the sample. Some embodiments may includeserum separator gel or plasma separator gel such as but not limited topolyester-based separator gels available from Becton Dickinson.

Optionally, one or more solid substrates may be provided within thesample vessel. For example, one or more beads or particles may beprovided within the sample vessel. The beads and/or particles may becoated with reagents or any other substance described herein. The beadsand/or particles may be capable of dissolving in the presence of thesample. The beads and/or particles may be formed from one or morereagents or may be useful for treating the sample. A reagent may beprovided in a gaseous form within the sample vessel. The sample vesselmay be sealed. The sample vessel may remain sealed before the sample isintroduced into the sample vessel, after the sample has been introducedto the sample vessel, and/or while the sample is being introduced intothe sample vessel. In one embodiment, the sample vessels may have smoothsurfaces and/or round bottoms. This is helpful to minimize the stress onthe blood sample, especially during centrifugation. Of course, inalternative embodiments, other shapes of the bottom of the sample vesselare not excluded.

In embodiments, a bodily fluid sample in a sealed sample vessel mayretain dissolved gases in the bodily fluid sample, such that samplestored in the sealed sample vessel retains a dissolved gas compositionsimilar to or the same as that of bodily fluid sample freshly extractedfrom a subject's body or of a freshly prepared from a different sample(e.g. plasma freshly prepared from whole blood). In embodiments, abodily fluid sample in a sealed sample vessel may retain at least 99%,98%, 95%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, or 20% of a dissolved gasover 10 minute, 20 minute, 30 minute, 45 minute, 1 hour, 2 hour, 4 hour,6 hour, 8 hour, 12 hour, 16 hour, 24 hour, 48 hour, or 72 hour timeperiod. In such embodiments, typically, the time period starts at thetime of depositing a sample into a sample vessel or the time of sealingthe sample vessel. To facilitate the preservation of dissolved gases ina bodily fluid sample, the sample may be stored in a sealed samplevessel at a selected temperature, such as, for example, 20 C, 15 C, 10C, 4 C, or at a freezing temperature below 0 C. Other temperatures forsample storage are not excluded.

Similarly, in embodiments, a bodily fluid sample in a sealed samplevessel may retain analytes in the bodily fluid sample, such that samplestored in the sealed sample vessel retains an analyte compositionsimilar to or the same as that of bodily fluid sample freshly extractedfrom a subject's body or of a freshly prepared bodily fluid sample (e.g.plasma freshly prepared from whole blood). In embodiments, a bodilyfluid sample in a sealed sample vessel may retain at least 99%, 98%,95%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, or 20% of an analyte over 10minute, 20 minute, 30 minute, 45 minute, 1 hour, 2 hour, 4 hour, 6 hour,8 hour, 12 hour, 16 hour, 24 hour, or 48 hour time period. In suchembodiments, typically, the time period starts at the time of depositinga sample into a sample vessel or the time of sealing the sample vessel.To facilitate the preservation of one or more analytes in a bodily fluidsample, the sample may be stored in a sealed sample vessel at a selectedtemperature, such as, for example, 20 C, 15 C, 10 C, 4 C, or at afreezing temperature below 0 C. Other temperatures for sample storageare not excluded. Optionally, a sample vessel may be centrifuged after asample is introduced into the vessel. For example, a sample vessel maybe centrifuged within 30 seconds, 1 minute, 2 minutes, 3 minutes, 4minutes, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 45minutes, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 2 days, 3 days, 4days, 5 days, 7 days, or 10 days of introduction of the sample into thevessel. Centrifuging a sample vessel containing a sample may, forexample, in the case of a whole blood sample, facilitate the separationof blood cells from plasma, to yield plasma and pelleted cells. In somecircumstances, centrifuging a sample increases the stability of one ormore analytes in blood or plasma.

FIG. 18F further shows that the sample vessels may each have at leastone information storage unit associated with the sample vessels.Optionally, some embodiments may have one information storage unitconvey information about a plurality of sample vessels, particularly(but not exclusively) in cases where the sample vessels all containsample from the same subject. Such an information storage unit could beon the carrier that holds the multiple sample vessels, instead of beingon the sample vessels themselves.

FIG. 18F shows a bottom-up view of an underside of one of the samplevessels that in one nonlimiting example, the information storage unit1860 may be at least one of: a barcode (e.g., 1-D, 2-D, or 3-D), quickresponse (QR) code, image, shape, word, number, alphanumeric string,color, or any combination thereof, or any type of visual informationstorage unit. Others may use information storage units that are not inthe visible spectrum. Others may use RFID tags, RF information storageunits, IR emitting tags, or other markers that do not rely onidentification through signals sent through the visual spectrum. Ofcourse, the information storage unit 1860 may also be positioned to beon a top end surface of the sample vessel. FIG. 18G shows that,optionally, an information storage unit 1860 may also be included on aside surface of the sample vessel. This may be in addition to or inplace of the top or bottom positioned information storage unit(s) 1860.

In one non-limiting example, information storage unit 1860 may be usedto identify sample and/or types of sample in a sample collection device.Optionally, there may be one or more information storage units persample vessel. Some may also use information storage units on the samplevessel holders. Information storage units may identify the samplecollection device, one or more individual sample vessels within thedevice, or components of the device. In some instances, the samplecollection device, a portion of the sample collection device, and/or thesample vessels may be transported. In one example, the sample collectiondevice or a portion of the sample collection device, may be transportedvia a delivery service, or any other service described elsewhere herein.The sample vessel may be delivered so that one or more tests may beperformed on the sample.

Optionally, the sample identity and/or the identity of the individualwho provided the sample could be tracked. By way of non-limitingexample, information associated with the individual or individuals(e.g., name, contact information, social security number, birth date,insurance information, billing information, medical history) and otherinformation of who provided the sample may be included. In someinstances, the type of sample (e.g., whole blood, plasma, urine, etc.)may be tracked. Optionally, the types of reagents that the sample willhave encountered (e.g., anticoagulants, labels, etc.) could also betracked. Additional information about the sample collection, such asdate and/or time of collection, circumstances under which sample wascollected, types of tests to be run on the sample, setting(s) for thetests, test protocols, insurance information, medical recordsinformation, or any other type of information may be considered.

In at least one or more embodiments described herein, informationstorage units may assist with tracking such information. The informationstorage units may be associated with such information. Such informationmay be stored off-board the sample collection device, on-board thesample collection device, or any combination thereof. In some instances,the information may be stored on one or more external devices, such asservers, computers, databases, or any other device having a memory. Insome instances, the information may be stored on a cloud computinginfrastructure. One or more resources that store the information may bedistributed over the cloud, through the internet from a remote server,wireless to a remote computer processor, or the like. In some instances,a peer-to-peer infrastructure may be provided. The information may bestored in the information storage unit itself, or may be associated withthe information storage unit elsewhere, or any combination thereof.

Optionally, an information storage unit may provide uniqueidentification, or may provide a high likelihood of providing uniqueidentification. In some instances, the information storage unit may havea visible component. The information storage unit may be opticallydetectable. In some instances, the information storage unit may bediscernible using visible light. In some examples, the informationstorage unit may be a barcode (e.g., 1-D, 2-D, or 3-D), quick response(QR) code, image, shape, word, number, alphanumeric string, color, orany combination thereof, or any type of visual information storage unit.

In other embodiments, the information storage unit may be opticallydetectable via any other sort of radiation. For example, the informationstorage unit may be detectable via infrared, ultraviolet, or any othertype of wavelength of the electromagnetic spectrum. The informationstorage unit may utilize luminescence, such as fluorescence,chemiluminescence, bioluminescence, or any other type of opticalemission. In some instances, the information storage unit may be a radiotransmitter and/or receiver. The information storage unit may be aradiofrequency identification (RFID) tag. The information storage unitmay be any type of wireless transmitter and/or receiver. The informationstorage unit may send one or more electrical signal. In some instances,GPS or other location-related signals may be utilized with theinformation storage unit.

Optionally, an information storage unit may be and/or include an audiocomponent or acoustic component. The information storage unit may emit asound that may be discernible to uniquely identify the identifiedcomponent.

Optionally, the information storage unit may be detectable via anoptical detection device. For example, a bar code scanner may be capableof reading the information storage unit. In another example, a camera(e.g., for still or video images) or other image capture device may becapable of capturing an image of the information storage unit andanalyzing the image to determine the identification.

Optionally, the information storage units may be on the holder of thesample vessel(s). One or more indentation may be provided in the holder.The information storage unit may be located within the indentation. Theindentations may be on the bottom or side surface of the holder. In someembodiments, the holder may include one or more protrusion. Theinformation storage unit may be located on the protrusion. In someinstances, the information storage units may be provided on an exteriorsurface of the holder. The information storage units may alternativelybe positioned on an interior surface of the holder. The informationstorage units may be detected from outside the sample collection device.

In some embodiments, the information storage units may be on an exteriorsurface of the sample vessels or an interior surface of the samplevessels. The information storage units may be detectable from outsidethe sample vessels. In some embodiments, the information storage unitsmay be provided on a bottom surface of the sample vessels.

In one non-limiting example, the holder may include an opticallytransmissive portion. The optically transmissive portion may be on abottom of the holder or a side of the holder. For example, a transparentor translucent window may be provided. In another example, the opticallytransmissive portion may be a hole without requiring a window. Theoptically transmissive portion may permit a portion inside the holder tobe visible. The information storage units may be provided on an exteriorsurface of the holder on the optically transmissive portion, an interiorsurface of the holder but may be visible through the opticallytransmissive portion, or on an exterior or interior surface of thesample vessel but may be visible through the optically transmissiveportion. In some instances, the information storage unit may be providedon an interior surface of the sample vessel, but the sample vessel maybe optically transmissive so that the information storage unit isviewable through the sample vessel and/or optically transmissiveportion.

Optionally, the information storage unit may be a QR code, bar code, orother optical information storage unit that may be optically visible,such as but not limited to being visible from outside the samplecollection device. A QR code may be visible through an optical window,hole, or the like at the bottom of the holder of the sample collectiondevice. The QR code may be provided on the sample collection deviceholder or on a portion of the sample vessel visible through the holder.An image capturing device, such as a camera or scanner may be providedexternal to the sample vessels or the transport container, and may becapable of reading the QR code.

In some embodiments, a single or a plurality of QR codes or otherinformation storage units may be provided on a sample collection device.In some instances, each sample vessel may have at least one informationstorage unit, such as a QR code associated with it. In one example, atleast one window may be provided in a holder per sample vessel, and eachwindow may permit a user to view a QR code or other information storageunit. For example, two sample vessels may be housed within a holder,each of the sample vessels having an associated information storage unitdiscernible from outside the holder.

In some embodiments, the information storage units may be provided withsample vessels housed by the holder. Separating the holder from the restof the sample collection device may cause the sample vessels to beseparated from the rest of the sample collection device. The samplevessels may remain within the holder or may be removed from the holder.The information storage units may remain with the sample vessels even ifthey are removed from the holder. Alternatively, the information storageunits may remain with the holder even if sample vessels are removed. Insome instances, both the holder and sample vessels may have informationstorage units so that the sample vessels and holders may be individuallytracked and/or matched even when separated.

In some instances, any number of sample vessels may be provided withinthe sample collection device. Some embodiments may connect all of thesesample vessels to the sample collection device all at once. Optionally,the sample vessels may be coupled in a sequential or othernon-simultaneous manner. The sample vessels may be capable of receivingsample received from a subject. Each sample vessel may optionally have aunique information storage unit. The unique information storage unit maybe associated with any information relating to the sample, subject,device, or component of the device.

In some instances, each information storage unit for each sample vesselmay be unique or contain unique information. In other embodiments, theinformation storage unit on the sample vessel need not be unique.Optionally, some embodiments may have information unique for the device,for the subject, and/or for the type of sample. In some embodiments, theinformation on the information storage unit may be used to associateseveral sample vessels with the same subject or the same information.

In some embodiments, the information storage unit is attached to orotherwise associated (physically or by non-physical association such asdatabase pointer or linkage) with the sample vessel or groups of samplevessels at the collection appointment. If associated by group, theassociation can be based on all being from the same user or other factoras set forth herein. Optionally, some embodiments may have informationstorage units already on the sample vessels or groups of sample vessels.In one non-limiting example, the information storage unit providesidentifier information that is then associated with the subject at ornear the time of sample collection. In this example, the information onthe information storage unit remains the same but is then linked to thesubject. In another embodiment, the information on the informationstorage unit is changed to include information about the subject.Optionally, some embodiments may have both, wherein some information ischanged and some is not (but may be then associated with the subject orother information about the collection event such as time date or thelike).

Referring now to FIGS. 19A to 19C, various embodiments of a front end ofa sample collection device will now be described. FIG. 19A shows on viewof a front end of the sample collection device with openings 1103 and1105 for their respective channels. In the present embodiment, theopenings 1103 and 1105 are placed in close proximity to each other withthe divider wall 1910 between the openings 1103 and 1105. In onenon-limiting example, the thickness of divider wall 1910 is set to bethe minimum thickness that can be reliably formed through amanufacturing process used to form the sample collection device. In oneembodiment, wall thickness should be about 1-10 mm. In some embodiments,instead of being side by side, the openings 1103 and 1105 may be in atop-bottom configuration, diagonal configuration, or other configurationwhere the two openings are in close proximity to one another.

Referring now to FIG. 19B, this embodiment shows the openings 1910 and1912 configured to be coaxial, relative to one another. This coaxialconfiguration of openings 1910 and 1912 allows for greater overlapbetween the two openings.

Referring now to FIG. 19C, this embodiment is similar to that of FIG.19B except that instead of square shaped openings, these openings 1920and 1922 are round. It should be understood that any variety of shapesmay be used including but not limited to circular, elliptical,triangular, quadrilateral (e.g., square, rectangular, trapezoidal),pentagonal, hexagonal, octagonal, or any other cross-sectional shape. Ofcourse, it should be understood that different shapes can be used foreach opening and that a collection device need not have the samecross-sectional shape for all openings. Some embodiments may have a onecross-sectional shape for the opening but have a differentcross-sectional shape for channel downstream from the opening.

Single Channel Sample Collection Device

Referring now to FIGS. 20A-20B, although the embodiments herein aretypically described as sample collection devices with two separatechannels, it should be understood that some embodiments may use a singleentry channel 2010. This single entry channel 2010 may or may not becoated. Suitable coatings include but not are limited to ananti-coagulant, plasma, or other materials.

FIG. 20A shows that in this embodiment of sample collection device 2000,a tissue penetrating member 2112 can be mounted coaxially within thesingle entry pathway 2010. This allows the wound at the target tissue tobe formed in a manner that will be aligned with the single entry pathway2010. The tissue penetrating member 2012 can be activated by one of avariety of techniques such as but not limited to actuation upon pressinga trigger, actuation upon contact of the device front end with thetarget tissue, or by pressure once the device is pressed against thetarget tissue with sufficient pressure. After actuation, the tissuepenetrating member 2012 can remain in the single entry pathway 2010.Optionally, the tissue penetrating member 2012 may retract out of thesingle entry pathway 2010.

The sample fluid entering the sample collection device 2000 may splitinto two or more separate pathways 2014 and 2016 from the single entrypathway 2010. This enables the sample fluid to be split into at leasttwo portions from a sample collected from a single point of contact. Thetwo portions may optionally be held in two separate holding chambers2018 and 2020. These chambers may each have one or more adapter channels2022 and 2024 to transfer the sample fluid to the vessels such as butnot limited to vessels 1146 a and 1146 b. It should be understood thatthe holding chambers 2018 and 2020 and/or the vessels 1146 a and 1146 bmay contain anti-coagulant therein to prepare the sample fluid forprocessing.

Referring now to FIG. 20B, this embodiment shows that the single entrypathway 2010 with a tissue penetrating member 2012 therein that, afteractuation, is configured to remain in whole or in part within the singleentry pathway 2010. It should be understood that this embodiment may usea solid penetrating member or one that is hollow, with a lumen therein.

Referring now to FIG. 21, yet another embodiment of a sample collectiondevice 2030 will now be described. This embodiment shows a reducedlength single entry pathway 2032 with a tissue penetrating member 2012configured to extend outward from the pathway 2032. After actuation, thetissue penetrating member 2012 may be in the pathway 2032 or optionally,retracted to not be in the pathway 2032. The sample fluid entering thesample collection device 2030 may split into two or more separatepathways 2034 and 2036 from the single entry pathway 2032. This enablesthe sample fluid to be split into at least two portions from a samplecollected from a single point of contact. This embodiment shows that thepathways 2034 and 2036 remain in capillary channel configuration and donot enlarge to become chambers such as the embodiments of FIGS. 20A-20B.It should be understood that any of the embodiments herein may includeone or more fill indicators for the collection pathways and/or thevessels on the devices so that users can know when sufficient filllevels have been reached.

It should also be understood that due to the small sample volumecollected with vessels such as but not limited to vessels 1146 a and1146 b, the “pull” from reduced pressure, such as but not limited tovacuum pressure, in the vessels is minimally or not transferred into thebody of subject in a manner that may collapse or detrimentally reshapethe blood vessel or other lumen from which sample fluid is beingcollected. For example, pediatric and geriatric patients typically havesmall and/or weak veins that can collapse when traditional, large volumevacutainers are used, due the higher vacuum forces associated withdrawing larger sample volumes into those traditional vessels. In atleast one embodiment of the device, it will not have this problembecause it will not impart a vacuum (suction) force on the vein. In oneembodiment, the amount of vacuum force draws no more than 120 μL ofsample fluid into the vessel 1146 a. Optionally, the amount of vacuumforce draws no more than 100 μL into the vessel 1146 a. Optionally, theamount of vacuum force draws no more than 80 μL into the vessel 1146 a.Optionally, the amount of vacuum force draws no more than 60 μL into thevessel 1146 a. Optionally, the amount of vacuum force draws no more than40 μL into the vessel 1146 a. Optionally, the amount of vacuum forcedraws no more than 20 μL into the vessel 1146 a. In one embodiment, thistype of draw is performed without the use of a syringe and basedprimarily on pulling force from the vessels and any force from the fluidexiting the subject. Optionally, the shaped pathway through the deviceto draw sample that has reached an interior of the device can assist inreducing force transfer from the vessels 1146 a and 1146 b to thesubject's blood vessel or other body lumen. Some embodiments may useabout three-quarter vacuum or less in the small volume vessels listedabove to minimize hemolysis of the sample and to prevent collapsing ofblood vessel in the subject. Some embodiments may use about half vacuumor less in the small volume vessels listed above to minimize hemolysisof the sample and to prevent collapsing of blood vessel in the subject.Some embodiments may use about one quarter vacuum or less in the smallvolume vessels listed above to minimize hemolysis of the sample and toprevent collapsing of blood vessel in the subject. Vacuum herein is fullvacuum, relative to atmospheric pressure.

It should also be understood that, in one embodiment, the chambercross-sectional area in the device is greater than the cross-sectionaldiameter of the needle and/or flexible tubing used for drawing thebodily fluid from the subject. This further assists in reducing theforce transfer to the subject. The vacuum pull from the vessels aredrawing most immediately on liquid sample in the device, not directly onsample in the needle which is more proximate to the subject. The longerpathway, buffered by the larger volume chamber in the collection devicedampens the pull on the blood vessel in the subject. Additionally, theinitial peak force pull is substantially less in a small volume vesselversus a larger volume vessel that is also under vacuum. The duration ofthe “pull” is also longer to enable the larger amount of sample to enterthe vessel. In a smaller volume, a significant portion of the sample tobe collected is already in the device and there is less that is drawnfrom the subject that is not already in the device prior to beginningthe sample pull.

Referring now to FIG. 22, yet another embodiment of a sample collectiondevice will now be described. This embodiment shows a collection device2100 that has a connector 2102 such as but not limited to Luer connectorthat allows for connection to a variety of sample acquisition devicessuch as a tissue penetrating member, needle, or the like. Some Luerconnectors may use a press-fit to engage other connectors while someembodiments of the connector 2102 may include threads to facilitateengagement. FIG. 22 shows that in this current embodiment, a butterflyneedle 2104 is coupled to a fluid connection pathway 2106 such as butnot limited to a flexible tube that leads to a connector 2108 to connectthe sample acquisition features to the sample collection device 2100.The flexible tubing 2106 allows the needle portion 2104 to be locatedaway from but still operably fluidly coupled to the sample collectiondevice 2100. This allows for greater flexibility in terms of positioningof the needle 2104 to acquire sample fluid without having to also movethe sample collection device 2100. Optionally, some embodiments maydirectly couple the tissue penetrating member to the device 2100 withoutthe use of flexible tubing.

At least some or all of the embodiments can have a fill indicator suchas but not limited to a view window or opening that shows when sample ispresent inside the collection device and thus indicate that it isacceptable to engage the sample vessel(s). Optionally, embodiments thatdo not have a fill indicator are not excluded. Some embodiments mayoptionally include one or more vents, such as but not limited to a port,to allow air escape as the channels in the collection device are filledwith sample. In most embodiments, the filled sample vessel(s) may bedisconnected from the sample collection device after a desired filllevel is reached. Optionally, additional sample vessel(s) can be engagedto the sample collection device to collect additional amounts of bodilyfluid sample. Optionally, the interior conditions of the sample vesselsare such that the vessels has a reduced pressure configure to draw inonly a pre-determined amount of sample fluid.

FIG. 23 shows an exploded view of one embodiment of the samplecollection device 2100. In this non-limiting example, the portion 1130may be configured to hold the vessel holder 1140 and the portion withsampling device holder 2160. The device 2100 may include an anti-leakagedevice 2162 that can engage the open ends of the adapter channels 2022and 2024 to minimize sample loss through the open ends until the vesselsin holder 1140 are engaged to draw sample in any vessel(s) therein. Inthe current embodiment, the anti-leakage device 2162 covers at least twoadapter channels 2022 and 2024 and is configured to be movable. Thepresent embodiment of anti-leakage device 2162 is sized so that it canbe moved to uncover the openings on adapter channels 2022 and 2024 whilestill allowing the adapter channels 2022 and 2024 to engage thevessel(s) in the holder 1140.

Referring now to FIGS. 24 and 25, one embodiment of the sampling deviceholder 2160 is shown in more detail. FIG. 24 shows the sampling deviceholder 2160 as an assembled unit. FIG. 25 shows an exploded view of thesampling device holder 2160 with a first portion 2164 and a secondportion 2166. The adapter channels 2022 and 2024 are also show as beingremovable from the second portion 2166. Although this embodiment of thesampling device holder 2160 is shown as two separate portions, it shouldbe understood that some alternative embodiments can configure the sampledevice holder 2160 as a single unitary unit. Optionally, someembodiments may configure to have more than two portions that areassembled together to form the holder 2160. Optionally, some embodimentsmay create separate portions along a longitudinal axis 2165 or otheraxis of the holder 2160, instead of along a lateral axis of holder 2160this is shown by the separation in FIG. 25.

Referring now to FIGS. 26 through 28, various cross-sectional views ofembodiments of the sample device holder 2160 and the device 2100 areshown. FIG. 26 shows a cross-sectional view of the portions 2164 and2166. Although not being bound by any particular theory, the use of theseparation portions 2164 and 2166 can be selected simplifymanufacturing, particularly for forming the various internal channelsand chambers in the holder 2160. For example, at least one wall 2167 ofthe chamber can be formed in the first portion 2164 while complementarywalls 2168 of the chamber can be formed in the second portion 2166. FIG.27 shows a top-down end view of the portion 2166 with the wall 2168visible from the end view.

Referring now to FIG. 28, a cross-sectional view of the assembled device2100 will now be described. This FIG. 28 shows that sample entering thedevice through the connector 2102 will enter the common chamber 2170before leading to the adapter channels 2022 and 2024. From the adapterchannels 2022 and 2024, movement of the holder 1140 in the directionindicated by arrow 2172 will operably fluidically couple the vessels1146 a and 1146 b to the adapter channels 2022 and 2024, moving samplefrom the channels into the vessels. In the present embodiment, there issufficient space 2174 to allow for movement of the vessels 1146 a and1146 b to have the adapter channels 2022 and 2024 penetrate the caps ofthe vessels 1146 a and 1146 b so that the adapter channels 2022 and 2024are in fluid communication with the interior of the vessels 1146 a and1146 b. Although only two vessel and adapter channel sets are shown inthe figures, it should be understood that other configuration with moreor less sets of vessels and adapter channels can be configured for usewith a device such as that shown in FIG. 28.

Modular Sample Collection Device

Referring now to FIGS. 29A-29C, although the embodiments hereintypically describe sample collection device as having an adapter channelfor connecting the sample collection channels with the vessels, itshould be understood that embodiments without such configurations arenot excluded.

By way of non-limiting example in FIG. 29A, as previously suggestedherein, some embodiments may be without a discrete, separate adapterchannel. Herein the collection channel 2422 may connect directly to thevessel 2446 by way of relative motion between one or both of thoseelements as indicated by the arrow 2449.

By way of non-limiting example in FIG. 29B, one or more adapter channels2454 may be discrete elements not initially in direct fluidcommunication with either the collection channel 2422 or the vessels2446. Herein the collection channel 2422 may connect to the vessel 2446by way of relative motion between one or more of the collection channel,the adapter channel(s) 2454, or the vessel 2446 (sequentially orsimultaneously) to create a fluid pathway from the collection channelsthrough the one or more adapter channels into the vessels.

By way of non-limiting example in FIG. 29C, one or more adapter channels2454 may be elements initially in contact with the vessels 2446. Theadapter channels 2454 may not be directly in communication with theinterior or the vessels. Herein the collection channel 2400 may connectto the vessel by way of relative motion between one or more of thoseelements (sequentially or simultaneously) to create a fluid pathway fromthe collection channels through the one or more adapter channels intothe vessels. Some embodiments may have a septum, sleeve, sleeve withvent, or cover 2455 over the end of the collection channel which will beengaged by the adapter channel. The engagement of the various elementsmay also move the adapter channel 2454 into the interior of the vessel2446, as initially, the adapter channel 2454 may not be in fluidcommunication with the interior. Some embodiments herein may have morethan adapter channel and some embodiments may use adapter channels withpointed ends on both ends of the channel. There may be variations andalternatives to the embodiments described herein and that no singleembodiment should be construed to encompass the entire invention.

It should be understood that any of the embodiments herein could bemodified to include the features recited in the description for FIGS.29A-29C.

Sample Processing

Referring now to FIG. 30, one embodiment of bodily fluid samplecollection and transport system will now be described. FIG. 30 shows abodily fluid sample B on a skin surface S of the subject. In thenon-limiting example of FIG. 30, the bodily fluid sample B can becollected by one of a variety of devices. By way of non-limitingexample, collection device 1530 may be but is not limited to thosedescribed in U.S. Patent Application Ser. No. 61/697,797 filed Sep. 6,2012, which is fully incorporated herein by reference for all purposes.In the present embodiment, the bodily fluid sample B is collected by oneor more capillary channels and then directed into sample vessels 1540.By way of non-limiting example, at least one of the sample vessels 1540may have an interior that is initially under a partial vacuum that isused to draw bodily fluid sample into the sample vessel 1540. Someembodiments may simultaneously draw sample from the sample collectiondevice into the sample vessels 1540 from the same or differentcollection channels in the sample collection device. Optionally, someembodiments may simultaneous draw sample into the sample vessels

In the present embodiment after the bodily fluid sample is inside thesample vessels 1540, the sample vessels 1540 in their holder 1542 (oroptionally, removed from their holder 1542) are loaded into thetransport container 1500. In this embodiment, there may be one or moreslots sized for the sample vessel holder 1542 or slots for the samplevessels in the transport container 1500. By way of non-limiting example,they may hold the sample vessels in an arrayed configuration andoriented to be vertical or some other pre-determined orientation. Itshould be understood that some embodiments of the sample vessels 1540are configured so that they hold different amount of sample in each ofthe vessels. By way of non-limiting example, this can be controlledbased on the amount of vacuum force in each of the sample vessels, theamount of sample collected in the sample collection channel(s) of thecollection device, and/or other factors. Optionally, differentpre-treatments such as but not limited to different anti-coagulants orthe like can also be present in the sample vessels.

As seen in FIG. 30, the sample vessels 1540 are collecting sample at afirst location such as but not limited to a sample collection site. Byway of non-limiting example, the bodily fluid samples are thentransported in the transport container 1500 to a second location such asbut not limited to a receiving site such as but not limited to ananalysis site. The method of transport may be by courier, postaldelivery, or other shipping technique. In many embodiments, thetransport may be implemented by having a yet another vessel that holdsthe transport container therein. In one embodiment, the samplecollection site may be a point-of-care. Optionally, the samplecollection site is a point-of-service. Optionally, the sample collectionsite is remote from the sample analysis site.

Although the present embodiment of FIG. 30 shows the collection ofbodily fluid sample from a surface of the subject, other alternativeembodiments may use collection techniques for collecting sample fromother areas of the subject, such as by venipuncture, to fill the samplevessel(s) 1540. Such other collection techniques are not excluded foruse as alternative to or in conjunction with surface collection. Surfacecollection may be on exterior surfaces of the subject. Optionally, someembodiments may collect from accessible surfaces on the interior of thesubject. Presence of bodily fluid sample B on these surfaces may benaturally occurring or may occur through wound creation or othertechniques to make the bodily fluid surface accessible.

Referring now to FIG. 31, yet another embodiment is described hereinwherein bodily fluid sample can be collected from an interior of thesubject versus collecting sample that is pooled on a surface of thesubject. This embodiment of FIG. 31 shows a collection device 1550 witha hypodermic needle 1552 that is configured to collect bodily fluidsample such as but not limited to venous blood. In one embodiment, thebodily fluid sample may fill a chamber 1554 in the device 1550 at whichtime sample vessel(s) 1540 may be engaged to draw the sample into therespective vessel(s). Optionally, some embodiments may not have achamber 1554 but instead have very little void space other thanchannel(s), pathway(s), or tube(s) used to direct sample from the needle1552 to the sample vessel(s) 1540. For bodily fluid samples such asblood, the pressure from within the blood vessel is such that the bloodsample can fill the chamber 1554 without much if any assistance from thecollection device. Such embodiments may optionally include one or morevents, such as but not limited to a port, to allow air escape as thechannels in the collection device are filled with sample. Optionally,some embodiments may have, instead of tubing connection to a needle, adirect needle attach to the collection device 1550, similar to thatshown in FIG. 44 where the needle is rigidly or substantially rigidlyconnected to the collection device. Some embodiments may have aremovable connection, a releasable connection, a Luer connection, athreaded connection, or other needle connection technique that may bedeveloped in the future.

At least some or all of the embodiments can have a fill indicator suchas but not limited to a view window or opening that shows when sample ispresent inside the collection device and thus indicate that it isacceptable to engage the sample vessel(s) 1540. Optionally, embodimentsthat do not have a fill indicator are not excluded. The filled samplevessel(s) 1540 may be disconnected from the sample collection deviceafter a desired fill level is reached. Optionally, additional samplevessel(s) 1540 can be engaged to the sample collection device 1550 (or1530) to collect additional amounts of bodily fluid sample.

Point of Service System

Referring now to FIG. 32, it should be understood that the processesdescribed herein may be performed using automated techniques. Theautomated processing may be used in an integrated, automated system. Insome embodiments, this may be in a single instrument having a pluralityof functional components therein and surrounded by a common housing. Theprocessing techniques and methods for sedimentation measure can bepre-set. Optionally, that may be based on protocols or procedures thatmay be dynamically changed as desired in the manner described in U.S.patent application Ser. Nos. 13/355,458 and 13/244,947, both fullyincorporated herein by reference for all purposes.

In one non-limiting example as shown in FIG. 32, an integratedinstrument 2500 may be provided with a programmable processor 2502 whichcan be used to control a plurality of components of the instrument. Forexample, in one embodiment, the processor 2502 may control a single ormultiple pipette system 2504 that is movable X-Y and Z directions asindicated by arrows 2506 and 2508. The same or different processor mayalso control other components 2512, 2514, or 2516 in the instrument. Inone embodiment, tone of the components 2512, 2514, or 2516 comprises acentrifuge.

As seen in FIG. 32, control by the processor 2502 may allow the pipettesystem 2504 to acquire blood sample from cartridge 2510 and move thesample to one of the components 2512, 2514, or 2516. Such movement mayinvolve dispensing the sample into a removable vessel in the cartridge2510 and then transporting the removable vessel to one of the components2512, 2514, or 2516. Optionally, blood sample is dispensed directly intoa vessel already mounted on one of the components 2512, 2514, or 2516.In one non-limiting example, one of these components 2512, 2514, or 2516may be a centrifuge with an imaging configuration to allow for bothillumination and visualization of sample in the vessel. Other components2512, 2514, or 2516 perform other analysis, assay, or detectionfunctions.

All of the foregoing may be integrated within a single housing 2520 andconfigured for bench top or small footprint floor mounting. In oneexample, a small footprint floor mounted system may occupy a floor areaof about 4 m² or less. In one example, a small footprint floor mountedsystem may occupy a floor area of about 3 m² or less. In one example, asmall footprint floor mounted system may occupy a floor area of about 2m² or less. In one example, a small footprint floor mounted system mayoccupy a floor area of about 1 m² or less. In some embodiments, theinstrument footprint may be less than or equal to about 4 m², 3 m², 2.5m², 2 m², 1.5 m², 1 m², 0.75 m², 0.5 m², 0.3 m², 0.2 m², 0.1 m², 0.08m², 0.05 m², 0.03 m², 100 cm², 80 cm², 70 cm², 60 cm², 50 cm², 40 cm²,30 cm², 20 cm², 15 cm², or 10 cm². Some suitable systems in apoint-of-service setting are described in U.S. patent application Ser.Nos. 13/355,458 and 13/244,947, both fully incorporated herein byreference for all purposes. The present embodiments may be configuredfor use with any of the modules or systems described in those patentapplications.

Referring now to FIGS. 33 to 37, a still further embodiment of a samplecollection device will now be described. As seen in FIGS. 33 and 34, atleast one embodiment shows a sample collection region 2600 that has acapillary channel region and then a lower flow resistance region 2610that increases the cross-sectional area of the channel to provide forlower flow resistance and increased flow rates. In at least oneembodiment, this lower flow resistance region 2610 is still a capillarychannel, but one with lower flow resistance. Optionally, otherembodiments may increase the size wherein the sample flows therein butnot under capillary action. The increased size of the channel can alsobe used to store sample therein. By way of non-limiting example, thisstorage can be temporary during collection, longer term such as fortransport from collection site to refrigeration, from collection site toreceiving site, other location to location transport, or other purpose.One embodiment can be configured to have caps that go on both ends ofthe device so that sample is contained therein without need fortransferring to vessels 1146 a and 1146 b.

Because the joint between regions 2600 and 2610 can be located acrossthe mid-line 2620, this can also reduce the amount of bonding materialused to join the items together. It should be understood thatembodiments can have channels 2612 and 2614 be of the samecross-sectional size and/or be configured to contain the same orsubstantially same volume in the channel. Optionally, the channels 2612and 2614 can be configured to hold different volumes. The same may betrue for the channels as they continue into region 2610. Optionally,some embodiments may have different sizes when in region 2610 while havethe same in region 2600 or vice versa. Other configurations of sizes arenot excluded. Although the channels here are shown as linear, it shouldbe understood that for any of embodiments disclosed herein, someembodiments may have curved or other non-straight portion of thechannel(s).

The other parts are similar to those previously described herein withregards to the vessels 1146 a and 1146 b, adapter channels, frits,holders 130, etc. . . . . Wicking of both channels at the junction (bothfill times<6-secs) has been improved (step removed) and blood got in tothe channel easily and passed the junction area without need fortilting. The parts may be made of PMMA, PET, PETG, etc. . . . In thisembodiment, this can provide a 7.5× faster fill relative to a capillarychannel of one cross-sectional size because the increase in size ofchannel in region 2610 will allow for easier flow into this region.

The flow resistance decreases to the fourth power in region 2610 basedon changes in channel size as seen in the formula:

$\overset{.}{M} = {\frac{\pi\;{pg}}{32\mu}\left\lbrack {{\frac{\sigma}{\rho}\frac{D^{3}}{L}} + {\frac{H}{4}\frac{D^{4}}{L}}} \right\rbrack}$

It should be understood that once a desired amount of sample is in thechannel(s), some embodiments may be configured so that the sample can bemanipulated to be moved into a storage vessel. By way of non-limitingexample, this movement of sample can be by way of a pull force, a pushforce, or both. In one embodiment, pull force may be provided by avessel that has vacuum therein, a vessel with a plunger or other movablesurface that moves to increase volume and draw sample therein, or anactive vacuum force. In one embodiment, push force can be pressure fromair or other gas provided from behind a bolus or other fluid grouping.In embodiment, compressed gas, pressure from a cap with a seal aroundthe device being slid over the collection device, a syringe coupled toone end and apply gas pressure, or other force can be exerted to urgegas forward. Force being provided may be different from the motive forceused to collect the sample in the channel(s). Optionally, someembodiments may use, different motive force per channel. Optionally,some may use a different motive force in region 2600 relative to zone2610.

While the teachings has been described and illustrated with reference tocertain particular embodiments thereof, those skilled in the art willappreciate that various adaptations, changes, modifications,substitutions, deletions, or additions of procedures and protocols maybe made without departing from the spirit and scope of the invention.For example, with any of the above embodiments, it should be understoodthat the fluid sample may be whole blood, diluted blood, interstitialfluid, sample collected directly from the patient, sample that is on asurface, sample after some pre-treatment, or the like. Those of skill inthe art will understand that alternative embodiments may have more thanone vessel that may be sequentially operably coupled to the needle oropening of the channel to draw fluid in the vessel. Optionally, someembodiments may have the vessels configured to operably couple to thechannels simultaneously. Some embodiments may integrate a lancing deviceor other wound creation device with the sample collection device tobring targeted sample fluid to a tissue surface and then collect thesample fluid, all using a single device. By way of nonlimiting example,a spring actuated, mechanically actuated, and/or electromechanicallyactuated tissue penetrating member may be mounted to have a penetratingtip exiting near an end of the sample collection device near samplecollection channel openings so that the wound site that is created willalso be along the same end of the device as the collection openings.Optionally, an integrated device may have collection openings on onesurface and tissue penetrating elements along another surface of thedevice. In any of the embodiments disclosed herein, the first opening ofthe collection channel may have a blunt shape, which is configured tonot readily puncture human skin.

Additionally, the use of heat patches on the finger or other targettissue can increase blood flow to the target area and thus increase thespeed with which sufficient blood or other bodily fluid can be drawnfrom the subject. The heating is used to bring the target tissue toabout 40 C to 50 C. Optionally, the heat brings target tissue to atemperature range of about 44 to 47 C.

Furthermore, those of skill in the art will recognize that any of theembodiments as described herein can be applied to collection of samplefluid from humans, animals, or other subjects. Some embodiments asdescribed herein may also be suitable for collection of non-biologicalfluid samples. Some embodiment may use vessels that are not removablefrom the carrier. Some may have the fluid sample, after being metered inthe sample collection portion, be directed by the second motive force toa cartridge that is then placed into an analyte or other analysisdevice. Optionally, it should be understood although many embodimentsshow the vessels in the carriers, embodiments where the vessels are bareor not mounted in carrier are not excluded. Some embodiments may havethe vessels that are separate from the device and are only brought intofluid communication once the channels have reached minimum fill levels.For example, the vessels may be held in a different location and areonly brought into contact by a technician once sufficient amount ofblood or sample fluid is in the sample collection device. At that time,the vessels may be brought into fluid communication simultaneously orsequentially to one or more of the channels of the sample collectiondevice.

Additionally, concentrations, amounts, and other numerical data may bepresented herein in a range format. It is to be understood that suchrange format is used merely for convenience and brevity and should beinterpreted flexibly to include not only the numerical values explicitlyrecited as the limits of the range, but also to include all theindividual numerical values or sub-ranges encompassed within that rangeas if each numerical value and sub-range is explicitly recited. Forexample, a size range of about 1 nm to about 200 nm should beinterpreted to include not only the explicitly recited limits of about 1nm and about 200 nm, but also to include individual sizes such as 2 nm,3 nm, 4 nm, and sub-ranges such as 10 nm to 50 nm, 20 nm to 100 nm, etc.. . .

Transport Container

Referring now to FIGS. 38A-38B, an exploded perspective view is shown ofone non-limiting example of a transport container 3200 provided inaccordance with one embodiment described herein. It should be understoodthat the transport container 3200 may be configured to have one or morefeatures of any other transport container described elsewhere herein. Byway of non-limiting example, the transport container 3200 may be usefulfor transporting one or more sample vessels therein. In someembodiments, the transport container 3200 provides a thermallycontrolled interior area to minimize undesired thermal decomposition ofthe sample during transport to another location, such as but not limitedto an analysis facility. It should be understood that the transportcontainer may be placed inside one or more other vessels duringtransport.

In one embodiment, the sample vessels may be provided from a samplecollection device that collected the bodily fluid sample. By way ofnon-limiting example, the sample vessels may contain sample therein inliquid form. In most embodiments, liquid form also includes embodimentsthat are suspensions.

By way of non-limiting example, the transport container 3200 may haveany dimension. In some instances, the transport container 3200 may havea total volume of less than or equal to about 1 m³, 0.5 m³, 0.1 m³, 0.05m³, 0.01 m³, 1000 cm³, 500 cm³, 300 cm³, 200 cm³, 150 cm³, 100 cm³, 70cm³, 50 cm³, 30 cm³, 20 cm³, 15 cm³, 10 cm³, 7 cm³, 5 cm³, 3 cm³, 2 cm³,1.5 cm³, 1 cm³, 700 mm³, 500 mm³, 300 mm³, 100 mm³, 50 mm³, 30 mm³, 10mm³, 5 mm³, or 1 mm³. The footprint and/or a largest cross-sectionalarea of the transport container may be less than or equal to about 1 m²,0.5 m², 0.1 m², 0.05 m², 100 cm², 70 cm², 50 cm², 30 cm², 20 cm², 15cm², 10 cm², 7 cm², 5 cm², 3 cm², 2 cm², 1.5 cm², 1 cm², 70 mm², 50 mm²,30 mm², 10 mm², 5 mm², or 1 mm². In some instances, the transportcontainer may have a dimension (e.g., height, width, length, diagonal,or circumference) of less than or equal to about 1 m, 75 cm, 50 cm, 30cm, 25 cm, 20 cm, 15 cm, 12 cm, 10 cm, 9 cm, 8 cm, 7 cm, 6 cm, 5 cm, 4cm, 3 cm, 2 cm, 1 cm, 0.7 cm, 0.5 cm, 0.3 cm, or 1 mm. In someinstances, the largest dimension of the transport container may be nogreater than about 1 m, 75 cm, 50 cm, 30 cm, 25 cm, 20 cm, 15 cm, 12 cm,10 cm, 9 cm, 8 cm, 7 cm, 6 cm, 5 cm, 4 cm, 3 cm, 2 cm, 1 cm, 0.7 cm, 0.5cm, 0.3 cm, or 1 mm.

Optionally, the transport container may be lightweight. In someembodiments, the transport container may weigh less than or equal toabout 10 kg, 5, kg, 4 kg, 3 kg, 2 kg, 1.5 kg, 1 kg, 0.7 kg, 0.5 kg, 0.3kg. 100 g, 70 g, 50 g, 30 g, 20 g, 15 g, 10 g, 7 g, 5 g, 3 g, 2 g, 1 g,500 mg, 300 mg, 200 mg, 100 mg, 70 mg, 50 mg, 30 mg, 10 mg, 5 mg, or 1mg, with or without the sample vessels having sample therein.

As seen in FIGS. 38A and 38B, one embodiment of the transport containermay have a top cover 3210, a housing for a thermal regulating device3220, one or more insert trays for the transport containers 3230 a, 3230b, and a bottom plate 3240.

In one embodiment, the top cover 3210 has a substantially flat shapealthough other shapes are not excluded. The top cover 3210 may cover athermal regulating device such as but not limited to heater or coolercontained in the transport container. The top cover may or may not havethe same footprint as a housing 3220 for the thermal regulating device.A cooler, heater, or other thermal regulating device 3220 may beprovided within the transport container 3200. Optionally, the device3220 may be active or passive units. The thermal regulating device maykeep the sample vessels within the transport container 3200 at a desiredtemperature or below a predetermined threshold temperature. Optionally,the thermal regulating device may be any temperature control unit knownin the art. Optionally, the thermal regulating device may be capable ofheating and/or cooling. Optionally, the thermal regulating device may bea thermoelectric cooler. Optionally, the thermal regulating device maybe encased between the top cover and the housing for the cooler.

Optionally, the top cover and the housing may or may not form anairtight seal. The top cover and/or housing may be formed from amaterial with a desired thermal conductivity. For example, the housing3220 may have a selectable thermal conductivity. In one embodiment, thehousing may include an embedded phase change material (PCM) within thebox material, so the temperature is substantially uniform throughout.PCM holds a very good temperature profile. It is desirable not to havesupercooling of the sample, such as that associated with ice, which maycreate a negative drop to −5° C. PCM can be configured to control totemperature ranges above freezing. By way of nonlimiting example,thermal conductivity may be in the range between about 100-250 W/m/K(watts/meter/Kelvin). Optionally, each sample vessel will come intocontact with the PCM. Some embodiments may have one PCM for each layer.The PCM material may be flow molded into the transport containermaterial. Optionally, there may be a chamber for the PCM material.Optionally, gaps in the tray may be filled with PCM. The PCM can providea passive thermal control technique.

Optionally, the PCM may be incorporated into the injection moldingmaterial. In such an embodiment, the entire vessel may be a coolingmedium. This can also prevent leakage of PCM from chambers in thetransport container. Transport container size can also shrink when thePCM is directly integrated into the transport container material. Energydensity is greater since storage capacity per mass is increased. Mixingplastics with PCM material can be configured to have both strength andcooling. By way of non-limiting example, 30% of the material may be PCMand the remainder is plastic for rigidity. By way of non-limitingexample, between 20% to 40% of the material may be PCM while theremainder is another material such as but not limited to plastic formechanical rigidity. Some embodiments may use a blow-molded outer thatis filled with PCM or other material. Inner could be formed with adifferent technique as it is may not be critical for the interior to becosmetically appealing. Optionally, cast molding or other lowertemperature molding process could also be used in place of or incombination with injection molding of the PCM integrated transportcontainer material. Embedded PCM could also be in the trays. Someembodiments could be a tray that is much more thermally conductive toachieve even, uniform cooling profile. Optionally, the PCM material iscontained in a chamber inside the chassis of the transport container,wherein the wall of the chamber may be thinner than wall thickness ofother areas of the shipping box chassis.

In one embodiment, the transport container 3200 may also have each ofthe trays 3230 a and 3230 b configured so that any information storageunits on the sample vessels are easily readable without having to removethe sample vessels from the trays 3230 a and 3230 b. In one example, theholders have openings at the bottom that allow information storage unitson the bottom to be visualized while the sample vessels are still in thetrays 3230 a and 3230 b.

FIG. 39 shows a plurality of views of the transport container 3200. Someshow that the sample vessel holders in the trays 3230 a or 3230 b mayhave open bottoms such that any information storage unit, such as butlimited to a barcode or other information storage unit, can be read fromunderneath or other orientation that does not require that samplevessels be removed from the transport container 3200. Optionally, onlycertain portions of the transport container 3200 such as but not limitedto a layer, a tray, or the like is removed to obtain the desiredinformation. Optionally, bar codes or other information storage unitscan be accessed through one or more openings in the tray. That allowsfor bar code scanning of very small transport container. Optionally, onecould scan rows of sample vessels individually or can scan entire trayall at once. Optionally, a user can see all sample vessel holders.Optionally, a computer vision system can also scan to see if a step suchas centrifugation was completed. This can be at either end of theshipping process. The computer vision system can visualize the samplevessel and determine if the sample there is in a form that confirms thata desired step was completed. If it detects an error, the system caninform the user or the system of the issue and/or re-perform the missingand/or incorrectly performed step. Optionally, the holders may haveclosed bottoms and information may be on the sides or other surfaces ofthe transport container 3200.

In some embodiments, the shapes of the holders may also be designed tofollow the contours of the sample vessels 3134 therein to increasesurface area contact and improve thermal control of the sample vessels.Optionally, thermal control of the sample vessels may occur throughthermal transfer with tray and/or the PCM, but not in direct contactwith the PCM. Optionally, some sample vessels 3134 could also be indirect contact with the vessel and/or the PCM. The openings for thesample vessels and/or the holders may be in linear rows, in a honeycombpattern, or be in another pattern.

Referring now to FIGS. 40A and 40B, a transport container 3200 is shownfully assembled. FIG. 40B shows a plurality of sample vessels 3134 suchas those associated with the sample collection device. The samplevessels 3134 can all be from sample associated with one subject in whichcase an information storage unit associated with tray 3230 a can be usedto provide information about this group of samples. Optionally,individual sample vessels may still each have an information storageunit that is the same as that of the tray 3230 a or they may each beunique. Some embodiments may insert sample vessels from multiplesubjects into the same tray 3230 a. Optionally, some may only partiallyfill each tray. Some may fill each opening in the tray, but not everysample vessel will have sample therein (i.e. some may be empty samplevessels inserted to provide uniform thermal profile). These stackabletrays 3230 a may have closure devices that use elements such as but notlimited to magnets, mechanical latches, or other coupling mechanisms tocouple trays together. In some embodiments, magnets may be used toengage the tray holding the sample vessels to enable ease of openingduring automation of loading and unloading. Optionally, the user cannotremove the tray from the transport container. Optionally, the usercannot remove the tray from the transport container without the use of atool to release the tray. Some embodiments have a keying mechanism(magnetic or other technique). In this manner, the patient servicecenter can put sample in but cannot take it out. Optionally, someembodiments can have shaped openings selected so that one cannot put thesample vessels and/or their holders in the wrong way to prevent usererror.

In one embodiment, the loading and/or unloading may occur in atemperature regulated room or chamber to maintain samples in a desiredtemperature range. In one embodiment, it is desirable to have atemperature range between about 1° to 10° C. Optionally, it is desirableto have the temperature range between about 2° to 8° C. Optionally, itis desirable to have a temperature range between about 4° to 5° C.Optionally, the materials of the trays 230 a and 230 b may be used toprovide thermally controlled atmosphere for the sample vessels. Some useconvection to control thermal profile inside the transport container200.

FIG. 40B also shows that in this particular embodiment, there may be agroove 3232 for an o-ring or other seal that can provide a tightconnection between layers of the transport container. The system mayalso include closure mechanisms 3234 such as but not limited magneticclosure devices to maintain the stackable insert tray in the desiredposition. It should also be understood that some embodiments may havethrough-holes 3236 for wiring sensor(s) to detect conditions experiencedthe stackable insert tray during shipment.

FIG. 40C shows various perspective views of the embodiment of FIGS. 40Aand 40B when the various components such the stackable trays and thelids are joined together to form the transport container 3200. As seenin FIG. 40C, the transport container may be comprised of multiple layersof sample vessels or trays having sample vessels. Optionally, someembodiments may have only a single layer of sample vessels. Someembodiments may use actively cooling or thermal control in one or morelayers of the transport container 3200. By way of non-limiting example,one embodiment may have a thermo-electric cooler in the top layer.Optionally, some embodiments may use a combination of active and passivethermal control. By way of non-limiting example, one embodiment may havea thermal mass such as but not limited to a phase change material (PCM)that is already at a desired temperature. An active thermal control unitmay be included to keep the PCM in the desired temperature range.Optionally, some embodiments may use only a thermal mass such as but notlimited to a PCM to maintain temperature in a desired range.

Transport Container with Removable Tray

Referring now to FIG. 41, yet another embodiment of a transportcontainer will now be described. FIG. 41 shows a transport container3300 having a thermally-controlled interior 3302 that houses a tray 3304that can hold a plurality of sample vessels 3306 in an arrayconfiguration, wherein each of the vessels 3306 holds a majority of itssample in a free-flowing, non-wicked form and wherein there is about 1ml or less of sample fluid in each of the vessels. Optionally, there isabout 2 ml or less of sample fluid in each of the vessels. Optionally,there is about 3 ml or less of sample fluid in each of the vessels. Inone non-limiting example, the vessels are arranged such that there areat least two vessels in each transport container with sample fluid fromthe same subject, wherein at least a first sample includes a firstanticoagulant and a second sample includes a second anticoagulant in thematrix.

Although FIG. 41 shows the sample vessels 3306 are held in an arrayconfiguration, other predetermined configurations are not excluded. Somemay place the sample vessels into hinged, swinging, or other retainingmechanism in the tray that may allow for motion in one or two degrees offreedom. Some embodiments may place the sample vessels into a devicethat has first configuration during loading and then assumes a secondconfiguration to retain the sample vessels during transport. Someembodiments may place the sample vessels into a material that has firstmaterial property during loading and then assumes a second property suchas but not limited to hardening to retain the sample vessels duringtransport.

In some embodiments, the sample vessels are in holders 3310 and the tray3304 defines openings and/or cavities sized to fit the holders 3310 andnot the sample vessels. By way of non-limiting example, the holders 3310can be used to keep associated vessels 3306 physically together while inthe tray 3304. Some embodiments have the holders 3310 directlycontacting the tray 3304 so that the vessels are protected from directcontact with the tray 3304. In one non-limiting example, the tray canhold at least 100 vessels, or optionally, at least 50 holders eachhaving two vessels.

Referring still to FIG. 41, this embodiment of transport container 3300may have some retaining mechanism 3320 such as but not limited to clips,magnetic areas, or the like to hold the tray 3306. The retainingmechanism 3320 may be configured to hold the tray 3304 in a mannerreleasable when desired. Optionally, the retaining mechanism 3320 may beconfigured to hold the tray 3304 in an un-releasable manner. In theembodiment shown in FIG. 41, the retaining mechanism 3320 is shown asmagnetic and/or metallic members in tray 3304 that are attracted tometal and/or magnetic members in the transport container 3300. When thetransport container 3300 arrives at a processing facility, the tray 3304may be configured to be removed from the transport container 3300. Thiscan occur by use of one or more techniques including but not limited tousing strong magnets to engage the magnetic and/or metallic members intray 3304. Some embodiments may use grippers, hooks, or other mechanicalmechanisms to remove the tray 3304 from the transport container 3300.Some embodiments may use a combination of techniques to remove the tray3304. It should also be understood that some embodiments may opt toremove the vessels 3306 and/or the holders 3310 while the tray 3304remains in the transport container 3300. Some techniques may perform attwo or more of the foregoing techniques.

It should also be understood that the transport container 3300 mayitself be a cooling device, comprising a thermal control material suchas but not limited to ice, a PCM, or the like. Other embodiments maydirectly integrate the thermal control material into the material usedto form the transport container 3300. As seen in FIG. 41, someembodiments of the transport container 3300 may have a substantial voidspace 3324 in which one or more the thermal control material is housedor integrated therein.

Referring still to FIG. 41, the transport container 3300 may alsoinclude openings 3330 for attachment of hinges or other connectiondevices for covers or connections to other layers of the transportcontainer 3300. For ease of illustration, the cover and/or connectionsto the cover or other layer are not shown in FIG. 41. Although someembodiments may only use a single layer, it should be understood thatmulti-layer embodiments are not excluded.

Referring now to FIG. 42, an exploded perspective view of yet anotherembodiment of a transport container 3400 will now be described. Theembodiment of FIG. 42 is designed to hold a tray 3402 in the transportcontainer interior 3404. The exploded perspective view shows a pluralityof vessels 3406 in holders 3410 in a tray 3402. The tray 3402 may beconfigured to have some or all portions of the retention mechanism 3420similar to retention mechanisms 3320 in the tray 3402. It should also beunderstood that the tray 3402 may have one or more cutouts, protrusions,or features to allow the tray 3402 to be inserted into the interior in alimited number of pre-determined orientations. Some embodiments may beconfigured to only enable one orientation of the tray in the vessel.Some embodiments may be configured to only enable two possibleorientations of the tray in the vessel.

FIG. 42 shows that in one embodiment, the transport container 3400 maybe formed from two separate pieces 3430 and 3432. Optionally, someembodiment may be formed from three or more pieces. Optionally, someembodiment may be a single piece. The pieces 3430 and 3432 can haveopenings that filled by plugs 3434 and 3436. The interior 3438 of thetransport container 3400 can retain a thermal control material such asbut not limited to ice, a phase change material, or the like. Otherembodiments may directly integrate the thermal control material into thematerial used to form the transport container 3400.

In one instance, the interior 3433 of the piece 3432 can be filled witha thermal control material such as but not limited to a PCM. Optionally,one embodiment could use an active thermal control material such as butnot limited to a thermoelectric cooler to cool the interior.

Referring now to FIG. 43, yet another embodiment of the transportcontainer 3500 will now be described. FIG. 43 shows that the transportcontainer 3500 may include a lid 3502 for covering the features and/orsample vessels therein. In some embodiments, the lid 3502 may containthermal insulating material. Optionally, the lid 3502 may include athermal control unit to assist in keeping the interior of the transportcontainer 3500 within a desired temperature range. Optionally, someembodiments may configure lid 3502 to be a thermally conductive materialthat can be useful in keeping the interior of the transport container3500 within a desired temperature range through thermal transfer from anexternal thermal control source. By way of non-limiting example, thethermal control source may be a cooling source, a heating source, athermoelectric heat exchanger, or other thermal control device. Itshould also be understood that similar thermal control source such asbut not limited to a PCM or an active cooling device can also beincluded in the void space 3514 below the layer 3516.

It should be understood that the features 3512 for retaining holders3310, 3410, or other shaped holders for the vessels may be in a pieceseparate from the transport container or they can be integrally formedinside of the transport container. Optionally, the features 3512 can bepart of a tray such as the trays 3302 and 3402 shown in FIGS. 41 and 42.Such a tray can be fixed or removable from the transport container 3500.Retaining mechanisms 3520 may also be incorporated into the tray toallow it to be held in place during transport.

Sample Collection and Transport

In embodiments, provided herein are systems and methods for collectionor transport of small volumes of bodily fluid sample.

In embodiments, a sample vessel containing a small volume of bodilyfluid sample may be transported. The sample and sample vessel may haveany of the respective characteristics described elsewhere herein. Inembodiments, a sample vessel may contain less than or equal to 5 ml, 3ml, 4 ml, 2 ml, 1.5 ml, 1 ml, 750 μl, 500 μl, 400 μl, 300 μl, 200 μl,150 μl, 100 μl, 75 μl, 50 μl, 40 μl, 30 μl, 20 μl, 10 μl, or 5 μl bodilyfluid sample. In embodiments, a sample vessel may have an interiorvolume of less than or equal to 5 ml, 3 ml, 4 ml, 2 ml, 1.5 ml, 1 ml,750 μl, 500 μl, 400 μl, 300 μl, 200 μl, 150 μl, 100 μl, 75 μl, 50 μl, 40μl, 30 μl, 20 μl, 10 μl, or 5 In embodiments, a sample vessel may havean interior volume of less than or equal to 5 ml, 4 ml, 3 ml, 2 ml, 1.5ml, 1 ml, 750 μl, 500 μl, 400 μl, 300 μl, 200 μl, 150 μl, 100 μl, 75 μl,50 μl, 40 μl, 30 μl, 20 μl, 10 μl, or 5 μl, and may contain bodily fluidsample which fills at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%,95%, 98%, 99%, or 100% of the interior volume of the vessel. Inembodiments, the sample vessel may be sealed, for example, with a cap,lid, or membrane. Any of the vessel interior dimensions or sampledimensions described herein may apply to the interior dimensions of asealed sample vessel, or to the dimensions of a sample therein,respectively. In embodiments, a sealed sample vessel may have aninterior volume of less than or equal to 5 ml, 4 ml, 3 ml, 2 ml, 1.5 ml,1 ml, 750 μl, 500 μl, 400 μl, 300 μl, 200 μl, 150 μl, 100 μl, 75 μl, 50μl, 40 μl, 30 μl, 20 μl, 10 μl, or 5 μl, and it may contain bodily fluidsample which fills at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%,95%, 98%, 99%, or 100% the interior volume of the vessel, such that lessthan or equal to 2 ml, 1.5 ml, 1 ml, 750 μl, 500 μl, 400 μl, 300 μl, 200μl, 150 μl, 100 μl, 75 μl, 50 μl, 40 μl, 30 μl, 20 μl, 10 μl, 5 μl, 4μl, 3 μl, 2 μl, or 1 μl of air is present in the interior volume of thesealed vessel. Thus, for example, a sealed sample vessel may have aninterior volume of less than or equal to 300 μl and it may containbodily fluid sample which fills at least 90% of the interior volume ofthe vessel, such that less than or equal to 30 μL of air is present inthe interior volume of the sealed vessel. In another example, a sealedsample vessel may have an interior volume of less than or equal to 500μl and it may contain bodily fluid sample which fills at least 80% ofthe interior volume of the vessel, such that less than or equal to 100μL of air is present in the interior volume of the sealed vessel. Inanother example, a sealed sample vessel may have an interior volume ofless than or equal to 150 μl and it may contain bodily fluid samplewhich fills at least 98% of the interior volume of the vessel, such thatless than or equal to 3 μl of air is present in the interior volume ofthe sealed vessel.

In embodiments, sample vessels containing a sample may also contain ananticoagulant. The anticoagulant may be dissolved in the sample orotherwise present in the vessel (e.g. dried on one or more interiorsurfaces of the vessel or in solid form at the bottom of the vessel). Asample vessel containing a sample may have a “total anticoagulantcontent”, wherein the total anticoagulant content is the total amount ofanticoagulant present in the interior volume of the vessel, and includesanticoagulant dissolved in the sample (if any), as well as anticoagulantin the vessel which is not dissolved in the sample (if any). Inembodiments, a sample vessel containing a sample may contain no morethan 1 ml sample and have a total anticoagulant content of no more than3 mg EDTA, may contain no more than 750 μl sample and have a totalanticoagulant content of no more than 2.3 mg EDTA, may contain no morethan 500 μl sample and have a total anticoagulant content of no morethan 1.5 mg EDTA, may contain no more than 400 μl sample and have atotal anticoagulant content of no more than 1.2 mg EDTA, may contain nomore than 300 μl sample and have a total anticoagulant content of nomore than 0.9 mg EDTA, may contain no more than 200 μl sample and have atotal anticoagulant content of no more than 0.6 mg EDTA, may contain nomore than 150 μl sample and have a total anticoagulant content of nomore than 0.45 mg EDTA, may contain no more than 100 μl sample and havea total anticoagulant content of no more than 0.3 mg EDTA, may containno more than 75 μl sample and have a total anticoagulant content of nomore than 0.23 mg EDTA, may contain no more than 50 μl sample and have atotal anticoagulant content of no more than 0.15 mg EDTA, may contain nomore than 40 μl sample and have a total anticoagulant content of no morethan 0.12 mg EDTA, may contain no more than 30 μl sample and have atotal anticoagulant content of no more than 0.09 mg EDTA, may contain nomore than 20 μl sample and have a total anticoagulant content of no morethan 0.06 mg EDTA, may contain no more than 10 μl sample and have atotal anticoagulant content of no more than 0.03 mg EDTA, or may containno more than 5 μl sample and have a total anticoagulant content of nomore than 0.015 mg EDTA. In embodiments, a sample vessel containing asample may contain no more than 1 ml sample and have a totalanticoagulant content of no more than 2 mg EDTA, may contain no morethan 750 μl sample and have a total anticoagulant content of no morethan 1.5 mg EDTA, may contain no more than 500 μl sample and have atotal anticoagulant content of no more than 1 mg EDTA, may contain nomore than 400 μl sample and have a total anticoagulant content of nomore than 0.8 mg EDTA, may contain no more than 300 μl sample and have atotal anticoagulant content of no more than 0.6 mg EDTA, may contain nomore than 200 μl sample and have a total anticoagulant content of nomore than 0.4 mg EDTA, may contain no more than 150 μl sample and have atotal anticoagulant content of no more than 0.3 mg EDTA, may contain nomore than 100 μl sample and have a total anticoagulant content of nomore than 0.2 mg EDTA, may contain no more than 75 μl sample and have atotal anticoagulant content of no more than 0.15 mg EDTA, may contain nomore than 50 μl sample and have a total anticoagulant content of no morethan 0.1 mg EDTA, may contain no more than 40 μl sample and have a totalanticoagulant content of no more than 0.08 mg EDTA, may contain no morethan 30 μl sample and have a total anticoagulant content of no more than0.06 mg EDTA, may contain no more than 20 μl sample and have a totalanticoagulant content of no more than 0.04 mg EDTA, may contain no morethan 10 μl sample and have a total anticoagulant content of no more than0.02 mg EDTA, or may contain no more than 5 μl sample and have a totalanticoagulant content of no more than 0.01 mg EDTA. In embodiments, asample vessel containing a sample may contain no more than 1 ml sampleand have a total anticoagulant content of no more than 30 USPharmacopeia (USP) units heparin, may contain no more than 750 μl sampleand have a total anticoagulant content of no more than 23 USP unitsheparin, may contain no more than 500 μl sample and have a totalanticoagulant content of no more than 15 USP units heparin, may containno more than 400 μl sample and have a total anticoagulant content of nomore than 12 USP units heparin, may contain no more than 300 μl sampleand have a total anticoagulant content of no more than 9 USP unitsheparin, may contain no more than 200 μl sample and have a totalanticoagulant content of no more than 6 USP units heparin, may containno more than 150 μl sample and have a total anticoagulant content of nomore than 4.5 USP units heparin, may contain no more than 100 μl sampleand have a total anticoagulant content of no more than 3 USP unitsheparin, may contain no more than 75 μl sample and have a totalanticoagulant content of no more than 2.3 USP units heparin, may containno more than 50 μl sample and have a total anticoagulant content of nomore than 1.5 USP units heparin, may contain no more than 40 μl sampleand have a total anticoagulant content of no more than 1.2 USP unitsheparin, may contain no more than 30 μl sample and have a totalanticoagulant content of no more than 0.9 USP units heparin, may containno more than 20 μl sample and have a total anticoagulant content of nomore than 0.6 USP units heparin, may contain no more than 10 μl sampleand have a total anticoagulant content of no more than 0.3 USP unitsheparin, or may contain no more than 5 μl sample and have a totalanticoagulant content of no more than 0.15 USP units heparin. Inembodiments, a sample vessel containing a sample may contain no morethan 1 ml sample and have a total anticoagulant content of no more than15 USP units heparin, may contain no more than 750 μl sample and have atotal anticoagulant content of no more than 11 USP units heparin, maycontain no more than 500 μl sample and have a total anticoagulantcontent of no more than 7.5 USP units heparin, may contain no more than400 μl sample and have a total anticoagulant content of no more than 6USP units heparin, may contain no more than 300 μl sample and have atotal anticoagulant content of no more than 4.5 USP units heparin, maycontain no more than 200 μl sample and have a total anticoagulantcontent of no more than 3 USP units heparin, may contain no more than150 μl sample and have a total anticoagulant content of no more than 2.3USP units heparin, may contain no more than 100 μl sample and have atotal anticoagulant content of no more than 1.5 USP units heparin, maycontain no more than 75 μl sample and have a total anticoagulant contentof no more than 1.2 USP units heparin, may contain no more than 50 μlsample and have a total anticoagulant content of no more than 0.75 USPunits heparin, may contain no more than 40 μl sample and have a totalanticoagulant content of no more than 0.6 USP units heparin, may containno more than 30 μl sample and have a total anticoagulant content of nomore than 0.45 USP units heparin, may contain no more than 20 μl sampleand have a total anticoagulant content of no more than 0.3 USP unitsheparin, may contain no more than 10 μl sample and have a totalanticoagulant content of no more than 0.15 USP units heparin, or maycontain no more than 5 μl sample and have a total anticoagulant contentof no more than 0.08 USP units heparin.

In embodiments, two or more sample vessels containing sample from asingle subject may be obtained or transported. When two or more samplevessels containing sample from a single subject are obtained ortransported, the two or more sample vessels may be stored or transportedin a vessel that does or does not contain samples from other subjects.In embodiments, at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 sample vesselscontaining sample from a single subject may be obtained or transported.In embodiments, no more than 2, 3, 4, 5, 6, 7, 8, 9, or 10 samplevessels containing sample from a single subject may be obtained ortransported. In embodiments, at least 2, 3, 4, 5, 6, 7, 8, or 9 samplevessels and no more than 3, 4, 5, 6, 7, 8, 9, or 10 sample vesselscontaining sample from a single subject may be obtained or transported.In embodiments involving two or more sample vessels containing samplefrom the same subject, the sample in each sample vessel may be obtainedfrom a subject at the same or at different times. In some embodimentsinvolving two or more sample vessels containing sample from the samesubject, the sample in each sample vessel may be from the same locationor source site on the subject. For example, two sample vesselscontaining whole blood from the same subject may be obtained, in whichboth sample vessels contain whole blood from the same fingerstick site.In other embodiments involving two or more sample vessels containingsample from the same subject, the sample in each sample vessel be from adifferent location/source site on the subject. For example, two samplevessels containing whole blood from the same subject may be obtained, inwhich one sample vessel contains whole blood from a first fingersticksite (e.g. on a first digit) and a second sample vessel contains wholeblood from a second fingerstick site (e.g. on a second digit). Inembodiments involving two or more sample vessels containing sample froma single subject, the two or more sample vessels may contain differenttypes of anticoagulants or other blood additives. For example, a firstsample vessel may contain whole blood with EDTA and a second samplevessel may contain whole blood with heparin, wherein the samples arefrom the same subject. In another example, a first and second samplevessel may contain whole blood with EDTA and a third sample vessel maycontain whole blood with heparin, wherein the samples are from the samesubject. In another example, a first sample vessel may contain wholeblood with EDTA, a second sample vessel may contain whole blood withheparin, and a third sample vessel may contain whole blood with sodiumcitrate, wherein the samples are from the same subject. In embodimentsinvolving two or more sample vessels containing sample from a singlesubject, the two or more sample vessels may contain different types ofsample from the subject. For example, a first sample vessel may containwhole blood and a second sample vessel may contain plasma from the samesubject. In another example, a first sample vessel may contain wholeblood and a second sample vessel may contain urine from the samesubject. In another example, a first and second sample vessel maycontain whole blood and a third sample vessel may contain saliva fromthe same subject.

In systems and methods provided herein, a total volume of bodily fluidsample may be obtained from a subject. The total volume of bodily fluidsample may be transferred into a single sample vessel, or into two ormore sample vessels. For example, a total volume of 500 microliters ofbodily fluid sample may be obtained from a subject, and it may betransferred into a single sample vessel, wherein the single samplevessel has a maximum interior volume of 600 microliters. In anotherexample, a total volume of 500 microliters of bodily fluid sample may beobtained from a subject, and it may be transferred into a two samplevessels, wherein each sample vessel has a maximum interior volume of 300microliters. In another example, a total volume of 500 microliters ofbodily fluid sample may be obtained from a subject, and it may betransferred into a two sample vessels, wherein one sample vessel has amaximum interior volume of 400 microliters and one sample vessel has amaximum interior volume of 100 microliters. In systems and methodsprovided herein, a total volume of bodily fluid sample of less than orequal to 5 ml, 4 ml, 3 ml, 2 ml, 1.5 ml, 1 ml, 750 μl, 500 μl, 400 μl,300 μl, 200 μl, 150 μl, 100 μl, 75 μl, 50 μl, 40 μl, 30 μl, 20 μl, 10μl, 5 μl or 1 μl may be obtained from a subject. The total volume ofbodily fluid sample from the subject may be divided between 1, 2, 3, 4,5, 6, 7, 8, 9, 10 or more sample vessels, as described elsewhere herein.When a total volume of a bodily fluid sample from a subject is dividedbetween two or more sample vessels, portions of the total volume ofbodily fluid sample in some or all of the different sample vessels maycontain different anticoagulants or other additives. For example, atotal volume of 500 microliters of bodily fluid sample may be obtainedfrom a subject, and it may be transferred into a two sample vessels,wherein one sample vessel contains 250 microliters of the bodily fluidsample mixed with EDTA, and one sample vessel contains 250 microlitersof the bodily fluid sample mixed with heparin. Typically, as usedherein, a total volume of bodily fluid sample refers to a single type ofbodily fluid sample—e.g. whole blood or urine or saliva, etc.

In embodiments, a sample vessel containing whole blood may becentrifuged before it is stored or shipped, such that the whole blood isseparated into plasma and pelleted cells in the sample vessel before itis shipped. In other embodiments, a sample vessel containing whole bloodis not centrifuged before it is stored or shipped.

In some embodiments of systems and methods provided herein, a bodilyfluid sample may be dried after it is collected and before it istransported. In embodiments, a dried sample may later be reconstitutedinto liquid form, such as at a time of analysis or processing of thesample.

In embodiments of systems and methods provided herein, a sample vesselmay be transported from a first location to a second location. A firstlocation may be a location where a sample is collected from a subject,and a second location may be a location where one or more steps areperformed for processing or analyzing the sample. The sample and samplevessel may have any of the respective characteristics describedelsewhere herein. For example, the sample may be in a liquid,non-matrixed, non-wicked form. The sample vessel may be transported in atransport container as described herein or other structure. For examplein some optional embodiments, a sample vessel may be transported in abag, pouch, envelope, box, capsule, or other structure. In embodiments,the first location and the second location may be within the same room,building, campus, or collection of buildings. In embodiments, a firstlocation and second location may be separated by at least 1 meter, 5meters, 10 meters, 50 meters, 100 meters, 500 meters, 1 kilometer, 5kilometers, 10 kilometers, 15 kilometers, 20 kilometers, 30 kilometers,50 kilometers, 100 kilometers, or 500 kilometers. In embodiments, afirst location and second location may be separated by no more than 5meters, 10 meters, 50 meters, 100 meters, 500 meters, 1 kilometer, 5kilometers, 10 kilometers, 15 kilometers, 20 kilometers, 30 kilometers,50 kilometers, 100 kilometers, 500 kilometers, or 1000 kilometers. Inembodiments, a first location and second location may be separated by atleast 1 meter, 5 meters, 10 meters, 50 meters, 100 meters, 500 meters, 1kilometer, 5 kilometers, 10 kilometers, 15 kilometers, 20 kilometers, 30kilometers, 50 kilometers, 100 kilometers, or 500 kilometers and no morethan 5 meters, 10 meters, 50 meters, 100 meters, 500 meters, 1kilometer, 5 kilometers, 10 kilometers, 15 kilometers, 20 kilometers, 30kilometers, 50 kilometers, 100 kilometers, 500 kilometers, or 1000kilometers. In embodiments in which a first location is a location wherea sample is obtained from a subject, a sample vessel may be transportedfrom a first location to a second location within 48 hours, 36 hours, 24hours, 12 hours, 8 hours, 6 hours, 4 hours, 3 hours, 2 hours, 1 hour, 45minutes, 30 minutes, 15 minutes, 10 minutes, 5 minutes, 1 minute, or 30seconds of collection of the sample from the subject.

As used herein, a “sample receiving site” is a place where a transportedsample may be received, and wherein one or more steps may be performedwith the sample. For example, a sample which arrives at a samplereceiving site may be processed, analyzed, or handled at the samplereceiving site, for example, as part of a test or assay with the sample.A sample may be transported, for example, in any vessel or device asdescribed herein. In embodiments, a sample receiving site may containone or more sample processing devices, which may be used for processingor analyzing the sample. A sample processing device may be as describedin, for example, U.S. patent application Ser. No. 13/244,947 filed Sep.26, 2011, or as in any other document incorporated by referenceelsewhere herein. During the transport of a sample from a samplecollection site to a sample receiving site, the sample may pass throughany number of locations. In embodiments, a first location may be asample collection site and a second location may be a sample receivingsite.

Referring now to FIG. 44, one embodiment of bodily fluid samplecollection and transport will now be described. FIG. 44 shows a bodilyfluid sample B on a skin surface S of the subject. In the non-limitingexample of FIG. 44, the bodily fluid sample B can be collected by one ofa variety of devices. By way of non-limiting example, collection device3530 may be but is not limited to those described in U.S. PatentApplication Ser. No. 61/697,797 filed Sep. 6, 2012, which is fullyincorporated herein by reference for all purposes. In the presentembodiment, the bodily fluid sample B is collected by one or morecapillary channels and then directed into sample vessels 3540. By way ofnon-limiting example, at least one of the sample vessels 3540 may havean interior that is initially under a partial vacuum that is used todraw bodily fluid sample into the sample vessel 3540. Some embodimentsmay simultaneously draw sample from the sample collection device intothe sample vessels 3540 from the same or different collection channelsin the sample collection device. Optionally, some embodiments maysimultaneous draw sample into the sample vessels

In the present embodiment after the bodily fluid sample is inside thesample vessels 3540, the sample vessels 3540 in their holder 3542 (oroptionally, removed from their holder 3542) are loaded into thetransport container 3500. In this embodiment, there may be one or moreslots sized for the sample vessel holder 3542 or slots for the samplevessels in the transport container 3500. By way of non-limiting example,they may hold the sample vessels in an arrayed configuration andoriented to be vertical or some other pre-determined orientation. Itshould be understood that some embodiments of the sample vessels 3540are configured so that they hold different amount of sample in each ofthe vessels. By way of non-limiting example, this can be controlledbased on the amount of vacuum force in each of the sample vessels, theamount of sample collected in the sample collection channel(s) of thecollection device, and/or other factors. Optionally, differentpre-treatments such as but not limited to different anti-coagulants orthe like can also be present in the sample vessels.

As seen in FIG. 44, the sample vessels 3540 are collecting sample at afirst location such as but not limited to a sample collection site. Byway of non-limiting example, the bodily fluid samples are thentransported in the transport container 3500 to a second location such asbut not limited to a receiving site such as but not limited to ananalysis site. The method of transport may be by courier, postaldelivery, or other shipping technique. In many embodiments, thetransport may be implemented by having a yet another container thatholds the transport container therein. In one embodiment, the samplecollection site may be a point-of-care. Optionally, the samplecollection site is a point-of-service. Optionally, the sample collectionsite is remote from the sample analysis site.

Although the present embodiment of FIG. 44 shows the collection ofbodily fluid sample from a surface of the subject, other alternativeembodiments may use collection techniques for collecting sample fromother areas of the subject, such as by venipuncture, to fill the samplevessel(s) 3540. Such other collection techniques are not excluded foruse as alternative to or in conjunction with surface collection. Surfacecollection may be on exterior surfaces of the subject. Optionally, someembodiments may collect from accessible surfaces on the interior of thesubject. Presence of bodily fluid sample B on these surfaces may benaturally occurring or may occur through wound creation or othertechniques to make the bodily fluid surface accessible.

Referring now to FIG. 45, yet another embodiment is described hereinwherein bodily fluid sample can be collected from an interior of thesubject versus collecting sample that is pooled on a surface of thesubject. This embodiment of FIG. 45 shows a collection device 3550 witha hypodermic needle 3552 that is configured to collect bodily fluidsample such as but not limited to venous blood. In one embodiment, thebodily fluid sample may fill a chamber 3554 in the device 3550 at whichtime sample vessel(s) 3540 may be engaged to draw the sample into therespective vessel(s). Optionally, some embodiments may not have achamber 3554 but instead have very little void space other thanchannel(s), pathway(s), or tube(s) used to direct sample from the needle3552 to the sample vessel(s) 3540. For bodily fluid samples such asblood, the pressure from within the blood vessel is such that the bloodsample can fill the chamber 554 without much if any assistance from thecollection device. Such embodiments may optionally include one or morevents, such as but not limited to a port, to allow air escape as thechannels in the collection device are filled with sample.

At least some or all of the embodiments can have a fill indicator suchas but not limited to a view window or opening that shows when sample ispresent inside the collection device and thus indicate that it isacceptable to engage the sample vessel(s) 3540. Optionally, embodimentsthat do not have a fill indicator are not excluded. The filled samplevessel(s) 3540 may be disconnected from the sample collection deviceafter a desired fill level is reached. Optionally, additional samplevessel(s) 3540 can be engaged to the sample collection device 3550 (or530) to collect additional amounts of bodily fluid sample.

FIG. 46 shows a still further embodiment of a sample collection device3570. This embodiment described herein has a tissue penetrating portion3572 such as but not limited to a hypodermic needle with a handlingportion 3574. The handling portion 3574 can facilitate positioning ofthe tissue penetrating portion 3572 to more accurately enter the patientto a desired depth and location. In the present embodiment, the samplecollection vessel(s) 3540 are in a carrier 3576 that is not in directphysical contact with the tissue penetration portion 3572. A fluidconnection pathway 3578 such as but not limited to a flexible tube canbe used to connect the tissue penetrating portion 3572 with the samplecollection vessel(s) 3540. Some embodiments have the sample vessel(s)3540 configured to be slidable to only be in fluid communication withthe tissue penetrating portion 3572 upon control of the user. At leastsome or all of the embodiments can have a fill indicator such as but notlimited to a view window or opening that shows when sample is presentinside the collection device and thus indicate that it is acceptable toengage the sample vessel(s) 3540. Optionally, embodiments that do nothave a fill indicator are not excluded. Some embodiments may optionallyinclude one or more vents, such as but not limited to a port, to allowair escape as the channels in the collection device are filled withsample. In most embodiments, the filled sample vessel(s) 3540 may bedisconnected from the sample collection device after a desired filllevel is reached. Optionally, additional sample vessel(s) 3540 can beengaged to the sample collection device 3570 to collect additionalamounts of bodily fluid sample.

Sample Processing

Referring now to FIG. 47, a system view is shown of the transportcontainer 3500 having its contents unloaded after arriving at adestination location by unloading assembly 3600. In one embodiment,after the lid 3502 is positioned in an open position, the sample vesselsin the vessel 3500 can be removed from therein. By way of non-limitingexample, the removal may occur by removing an entire tray of the samplevessels, removing holders of multiple sample vessels from the tray,and/or by removing the sample vessels individually. Some embodiments mayuse a robotically controlled structure 3602 that can move vertically asindicated by arrow 3604 and/or horizontally as indicated by arrow 3606along a gantry 3608 to remove sample vessels from the transportcontainer 3500. A programmable process 3610 can be used to control theposition of the structure 3602 that is used to manipulate the samplevessels. In one embodiment, the structure 3602 includes a magnet forengaging the retention mechanisms to remove the tray from the structure3602. Other embodiments using robotic arms and/or other types ofprogrammable manipulators can be configured for use herein and are notexcluded.

In embodiments, upon the arrival of a sample vessel containing a sampleat a location for processing or analysis of the sample, the sample maybe removed from the sample vessel. The sample vessel may processed (e.g.shaken, rotated, mixed, or centrifuged) before the sample is removedfrom the sample vessel. Sample may be removed from the sample vessel byany appropriate mechanism, such as aspiration (e.g. by a fluid handlingsystem or pipette), pouring, or mechanical force (e.g. by forcing thesample from the vessel by reducing the dimensions of the interior regionof the sample vessel). In embodiments, upon the removal of the samplefrom the sample vessel, little or no sample remains behind in the vessel(e.g. as mechanical/transfer loss). For example, after the removal ofsample from the vessel, less than or equal to 50 μl, 40 μl, 30 μl, 20μl, 15 μl, 10 μl, 5 μl, 4 μl, 3 μl, 2 μl, 1 μl, or 0 μl of sample mayremain in the sample vessel.

By way of non-limiting example, the samples in the sample vessels canthen be processed using systems such as that described in U.S. patentapplication Ser. No. 13/244,947 filed Sep. 26, 2011, fully incorporatedherein by reference for all purposes. The analysis system can beconfigured in a CLIA compliant manner as described in U.S. patentapplication Ser. No. 13/244,946 filed Sep. 26, 2011, fully incorporatedherein by reference for all purposes. In embodiments, a sampletransported according to systems or methods provided herein may bedivided into two or more smaller portions upon arrival at location forprocessing or analysis, and various assays may be performed with thesample. For example, in embodiments, at least 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 20, 30, 40, or 50 assays may be performed with a sample transportedaccording to systems or methods provided herein. The assays may includeassays of different types (e.g. to assay for protein, nucleic acid, orcells), and use one or more detection methods (e.g. cytometry,luminescence, or spectrophotometer-based). In embodiments, two or moresample vessels containing sample from a single subject may betransported, wherein the two or more sample vessels contain at least twodifferent anticoagulants mixed with the sample (e.g. one sample vesselcontains EDTA-sample and one sample vessel contains heparin-sample).Sample from the EDTA-sample vessel may then be used for one or moreassays that are heparin-sensitive or EDTA-insensitive. Similarly, samplefrom the heparin-sample vessel may then be used for one or more assaysthat are EDTA-sensitive or heparin-insensitive. In embodiments, a sampletransported according to systems and methods provided herein may bedivided into two or more portions upon arrival at a destination, andanalyzed on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more different sampleanalyzers.

Referring now to FIGS. 49 to 51, it should be understood that at leastany two of the tests on the list (FIGS. 49 to 51) can be performed usinga sample from a subject prepared or transported according to a system ormethod provided herein. For example, at least two tests on the list maybe performed using a bodily fluid sample from a subject, wherein thetotal volume of bodily fluid sample used to perform the test is no morethan 300 microliters, and the total volume of bodily fluid sample fromthe subject is transported in liquid form a sample vessel having aninterior volume of 400 microliters or less. In another example, at leasttwo tests on the list may be performed using a bodily fluid sample froma subject, wherein the total volume of bodily fluid sample used toperform the tests is no more than 300 microliters, and the total volumeof bodily fluid sample from the subject is transported in liquid form ina first sample vessel and a second sample vessel, each vessel having aninterior volume of 200 microliters or less, the first sample vesselcontaining bodily fluid sample mixed with a first anticoagulant and thesecond sample vessel containing bodily fluid sample mixed with a secondanticoagulant. In embodiments, at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12, 13, 14, 15, 20, 25, 30, 35, 40, 50, or 60 of the tests on the list(FIGS. 49 to 51) may be performed using a bodily fluid sample from asubject having a total volume of no greater than or equal to 5 ml, 4 ml,3 ml, 2 ml, 1.5 ml, 1 ml, 750 μl, 500 μl, 400 μl, 300 μl, 200 μl, 150μl, 100 μl, 75 μl, 50 μl, 40 μl, 30 μl, 20 μl, 10 μl, 5 μl or 1 μl. Thetotal volume of the bodily fluid sample may be stored or transportedfrom a collection site to an analysis or processing location in a singlesample vessel, or it may be divided between 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 20, 25, or more sample vessels. When the totalvolume of a bodily fluid sample from a single subject is divided intotwo or more sample vessels, the sample portions in some or each of thesample vessels may contain a different anticoagulant or other additive.In an example, no more than a total volume of 300 microliters of bodilyfluid sample from a subject may be used for performing two or more ofthe tests, wherein at least one portion of the no more than 300microliter sample is mixed with first anti-coagulant and a secondportion of the no more than 300 microliter sample is mixed with a secondanti-coagulant different from the first. Optionally, each portion of theno more than 300 microliter sample is in its own sample vessel.Optionally, two or more of the tests may be performed, wherein all ofthe no more than 300 microliter sample is transported in a single vesseland contains a single anti-coagulant. Optionally, at least any three ofthe tests on that list can be conducted using no more than a totalvolume of 300 microliters of blood from a subject for all of the tests.Optionally, at least any five of the tests on that list can be conductedusing no more than a total volume of 300 microliters of blood from asubject for all of the tests. Optionally, at least any seven of thetests on that list can be conducted using no more than a total volume of300 microliters of blood from a subject for all of the tests.Optionally, at least any ten of the tests on that list can be conductedusing no more than a total volume of 300 microliters of blood from asubject for all of the tests. Optionally, at least any fifteen of thetests on that list can be conducted using no more than a total volume of300 microliters of blood from a subject for all of the tests.Optionally, at least any twenty of the tests on that list can beconducted using no more than a total volume of 300 microliters of bloodfrom a subject for all of the tests. For any of the above, in at leastsome embodiments, at least one portion is of a first anti-coagulant anda second portion is of a second anti-coagulant different from the first.

Referring now to FIG. 52, yet another embodiment is shown of a devicefor bodily fluid sample collection. FIG. 52 shows a bodily fluid sampleB on the subject being collected by a collection device 3710. As seen inFIG. 52, the collection device 3710 may include a collection portion3712 such as but not limited to capillary tube or other collectionstructure. The collection portion 3712 draws fluid therein, eventuallydirecting it towards an inner cavity 3714 of the device 3710. After thecollection portion 3712 has collected a desired amount, the entiredevice 3710 can be oriented as shown in FIG. 52 so that gravity can thendraw the sample into the cavity 3714. After all the sample B has beenmoved into the cavity 3714, the collection portion 3712 can be removedfrom device 3710. In one embodiment, the cap and the collection portion3712 is removed and replaced with a closed cap 3718. In one non-limitingexample, the cap 3718 can be one without any openings thereon.Optionally, some may have a septa or other closable opening in the cap,wherein the collection portion 3712 can be removed without having toreplace the cap with a new one of a different configuration.

Modular Sample Collection Device

Referring now to FIGS. 53A-53C, although the embodiments hereintypically describe sample collection device as having an adapter portion3750 for connecting the sample collection portion 3740 with the samplestorage vessels 3760, it should be understood that embodiments withoutsuch configurations are not excluded.

By way of non-limiting example in FIG. 53A, one or more adapter portion3750 may be discrete elements not initially in direct fluidcommunication with either the collection portion 3740 or the samplestorage vessels 3760. Herein the collection portion 3740 may connect tothe vessel 3760 by way of relative motion between one or more of thecollection portion, the adapter portion 3750, or the vessel(s) 3760(sequentially or simultaneously) to create a fluid pathway from thecollection channels through the one or more adapter channels into thevessels.

By way of non-limiting example in FIG. 53B, as previously suggestedherein, some embodiments may be without a discrete, separate adapterportion 3750. Herein the collection portion 3740 may connect directly tothe vessel 3760 by way of relative motion between one or both of thoseelements as indicated by the arrow 3770. As seen in FIG. 53B, there maybe a fluid flow feature 3780 that with relative motion between one orboth of those elements as indicated by the arrow 3782. In onenon-limiting example, this fluid flow feature 3780 can be a cap thatengages one end of the collection portion 3740 to encourage fluid flowin to the vessel 3760. Optionally, the fluid flow feature 3780 may be acap that has a front surface shaped to engage the collection portion3740. Optionally, the fluid flow feature 3780 may be a plunger, a rod,and/or other device to encourage flow towards the sample storage vessel3760. Optionally, the fluid flow feature 3780 is not fully engaged untilthe sample collection portion 3740 is ready to engage the vessel 3760.Optionally, some embodiments may be configured so that the flow fromcollection portion 3740 to sample storage vessel 3760 is without the useof the fluid flow feature 3780, but is instead based on a differentmotive force, such as but not limited to gravity, vacuum suction, orblowing force provided at the appropriate end of the collection portion3740.

By way of non-limiting example in FIG. 53C, one or more embodiment mayuse the collection portion 3740 as the storage vessel. Some embodimentsmay simply cap both ends with caps 3790 and 3792 once the desired filllevel is reached. As seen in Figure in FIG. 53C, the caps 3790 and 3792can hold the fluid therein, even when the portion 3740 is in a verticalorientation.

There may be variations and alternatives to the embodiments describedherein and that no single embodiment should be construed to encompassthe entire invention. For example, there can be two or more capillarytubes in the collection portion 3740. Optionally, they can be eachformed as discrete tubes or channels. Optionally, some may have a commoninitial portion but separate exits ports such as but not limited to a Yconfiguration. It should be understood that any of the embodimentsherein could be modified to include the features recited in thedescription for FIGS. 53A-53C.

Referring now to FIG. 54, after a sample vessel 3800 arrives at adesired processing destination, the sample in the vessel 3800 can beappropriately prepared. In one embodiment, the vessel 3800 is similar tothat of vessel 3710. As seen in FIG. 54, the sample can be processed toaliquot one portion into a processing device such as but not limited toan inlet on a cartridge 3802 and to another inlet on another cartridge3804. In one embodiment, both of the cartridges 3802 are microfluidicdiscs that process sample for blood chemistry testing such as but notlimited to Comprehensive Metabolic Panel (ALB, ALP, ALT, AST, BUN, Ca,Cl−, CRE, GLU, K+, Na+, TBIL, tCO2, TP), Basic Metabolic Panel (BUN, Ca,CRE, eGFR, GLU, Cl−, K+, Na+, tCO2) Lipid Panel (CHOL, HDL, CHOL/HDL,LDL, TRIG, VLDL, nHDLc); Lipid Panel Plus (tCHOL, HDL, CHOL/HDL Ratio,LDL, TRIG, VLDL, GLU, ALT, AST, nHDLc); Liver Panel Plus (ALB, ALP, ALT,AST, AMY, TBIL, TP, GGT); Electrolyte Panel (Cl−, K+, Na+, tCO2);General Chemistry (ALB, ALP, ALT, AMY, AST, BUN, Ca, CRE, eGFR, GGT,GLU, TBIL, TP, UA); General Chemistry 6 (ALT, AST, CRE, eGFR, GLU, BUN,GGT) Renal Function Panel (ALB, BUN, Ca, CRE, eGFR, GLU, Cl−, K+, Na+,tCO2 PHOS); Metlyte (Cl−, K+, Na+, tCO2, BUN, CK, CRE, eGFR, GLU);Kidney Function (BUN, CRE, eGFR; Hepatic Function Panel (ALB, ALP, ALT,AST, DBIL, TBIL, TP); Basic Metabolic Panel (BUN, Ca, CRE, eGFR, GLU,Cl−, K+, Na+, tCO2, Mg, LDH); MetLyte Plus CRP (Cl−, K+, Na+, tCO2, BUN,CK, CRE, eGFR, GLU, CRP); BioChemistry Panel Plus (ALB, ALP, ALT, AMY,AST, BUN, Ca, CRE, eGFR, CRP, GGT, GLU, TP, UA); MetLac (ALB, BUN, Ca,Cl−, CRE, GLU, K+, LAC, Mg, Na+, Phos, tCO2). It should be understoodthat other fluid handling technologies that may be developed in thefuture can also be adapted for use in at least one of the embodimentsherein. In some embodiments, the sample can be delivered to a generalchemistry microfluidic/centrifugal cartridge(s) 3802 (and/or 3804) usingtubing to carry the fluid to a destination such as but not limited tofluid receiving port on the cartridge. At least one or more othercartridges, such as but not limited to an open-fluid movement typecartridge as described in the applications incorporated by referenceherein, can also be used to improve the types of testing available.Although at least two destination cartridges are shown, it should beunderstood that embodiment with more than two are not excluded (as shownby the additional cartridge shown in phantom). Fluid transport may be byway of pipette, by fluidic tubing, microfluidics, or by other fluidhandling technologies that may be developed in the future.

Referring now to FIG. 55A, it should be understood that some embodimentscan use a sample handling system with pipette(s) or the like the extractthe sample in a tubeless manner from the vessel 3800. Althoughpipette(s) are described in this embodiment, it should be understoodthat other fluid handling technologies that may be developed in thefuture can also be adapted for use in at least one of the embodimentsherein. FIG. 55A shows that an automated system can be used to aliquotthe sample. It should also be understood that in some embodiments, priorto, during, or after aliquoting, there can be sample dilution toincrease the liquid volume of the sample. This can be beneficial forvarious purposes. FIG. 55A also shows that in some embodiments, thesample can be delivered to a general chemistry microfluidic/centrifugalcartridge(s) 3802 (and/or 3804). At least one or more other cartridges,such as but not limited to an open-fluid movement type cartridge asdescribed in the applications incorporated by reference herein, can alsobe used to improve the types of testing available. Although at least twodestination cartridges are shown, it should be understood thatembodiment with more than two are not excluded (as shown by theadditional cartridge shown in phantom). Fluid transport may be by way ofpipette, by fluidic tubing, microfluidics, or by other fluid handlingtechnologies that may be developed in the future. Some embodiments mayuse the same techniques to move sample to the cartridges or otherdestination(s), or optionally, some may use a combination of one or moreof the techniques to move the sample. By way of example and notlimitation, testing may involve using other detection techniques such asbut not limited to ELISA, nucleic acid amplification, microscopy,spectrophotometry, electrochemistry and/or other detection techniques toaugment the types of analysis that can be done, in addition to thegeneral chemistry testing using the cartridge 3802. Optionally, itshould be understood that more than one cartridge 3802 and/or individualunit cartridge 3806 can be used herein with the system of aliquotingfrom the vessel 3800.

Referring now to FIG. 55B, a still further embodiment is shown wherein avessel 3800 is shown having a sample fluid therein. In one example, thesample fluid therein may be “neat” or undiluted. Optionally, someembodiments may be configured so that sample may have been pre-processedat the collection site and/or at the receiving site to dilute the sampleand/or provide certain chemical material into the sample. As seen inFIG. 55B, a fluid handling system may use a pipette 3602 to aliquotsample from vessel 3800 to one or more other vessels 3810, 3812, and/or3814. By way of non-limiting example, these vessels 3810, 3812, or 3814may be the same vessel as that of vessel 3800. Optionally, they may bedifferent type of vessel. Based on bar code or other information aboutthe sample, the processor programmed to determine at least a desiredsample dilution for a sample and at least a desired number ofaliquot(s). In this non-limiting example, the aliquots are eachtransported to one sample processing unit 3820, 3822, and 3824. Thesemay all be the same type of processing unit, each may be a typedifferent from the other, or some may be the same and some different. Inat least one non-limiting example, the sample processing unit can besingle sample processor or a batch processor that can handle a pluralityof sample simultaneously.

FIG. 55C shows a still further embodiment wherein a sample is collectedat a collection site and then transported to a second site while sampleremains in liquid form. FIG. 55C shows that a plurality of vesselshaving sample can be collected from a single wound on the subject. Thisallows the subject to provide multiple samples that can be treated bydifferent types of chemicals in each of the vessels. FIG. 55C shows acourier that can transport a transport container that may includesamples from only one subject or multiple samples from multiple subjectsto a receiving site. Although a human courier is shown, it should beunderstood that robotic transports, drones, or other transporttechniques, systems, or devices that may be developed in the future arenot excluded (including but not limited to transport of “virtual”version(s) of the sample). In this non-limiting example, the receivingsite may load one or more vessels 1504 from the transport container intoa cartridge having independently movable reagent units and/or assayunits. This cartridge can then be loaded into one or more processingmodules 701 to 707. These units may be identical modules. Optionally, atleast one of the modules is different from the others. Similar to FIG.55B, some embodiments may include a processor 3830 that may coordinatedilution and/or aliquoting of sample from vessel 1504 (based on vesselID or other associated information) prior to loading the vessel 1504 orother vessel(s) that contain the sample and/or pre-diluted sample intothe cartridge. In at least one embodiment herein, each of the modulescan receive at least one cartridge and at least one sample vessel.Optionally, more than one sample vessel can be placed in each cartridge.Optionally, the sample vessels may contain different types of sample sothat cartridge can have more than one type of sample loaded into it.Optionally, some embodiments may have modules with at least onereceiving area for a cartridge and at least one receiving area for asample.

Optionally, some embodiments may have only one location for receiving acartridge which then also contains at least one sample. In this manner,a user has decreased risk of having to load separate items into themodule. Once loaded, at least one embodiment herein is configured sothat there is no more user manipulation of the sample once it isinserted in the module. This non-limiting example can be used minimizeerror associated with human factors once the sample is being processedin the module.

It should also be understood that some embodiments may handle aplurality of sample simultaneously using centrifugal or other force tobring the sample down to a settled level inside the sample vessels. Inone non-limiting example, this can be achieved by way of a traycentrifuge such as but not limited to a 384 well plate centrifuge.

FIG. 55C shows a system 700 having a plurality of modules 701-706 and acytometry station 707, in accordance with an embodiment of theinvention. The plurality of modules include a first module 701, secondmodule 702, third module 703, fourth module 704, fifth module 705 andsixth module 706.

The cytometry station 707 is operatively coupled to each of theplurality of modules 701-706 by way of a sample handling system 708. Thesample handling system 708 may include a pipette, such as a positivedisplacement, air displacement or suction-type pipette, as describedherein.

The cytometry station 707 includes a cytometer for performing cytometryon a sample, as described above and in other embodiments of theinvention. The cytometry station 707 may perform cytometry on a samplewhile one or more of the modules 701-706 perform other preparationand/or assaying procedure on another sample. In some situations, thecytometry station 707 performs cytometry on a sample after the samplehas undergone sample preparation in one or more of the modules 701-706.

The system 700 includes a support structure 709 having a plurality ofbays (or mounting stations). The plurality of bays is for docking themodules 701-706 to the support structure 709. The support structure 709,as illustrated, is a rack.

Each module is secured to rack 709 with the aid of an attachment member.In an embodiment, an attachment member is a hook fastened to either themodule or the bay. In such a case, the hook is configured to slide intoa receptacle of either the module or the bay. In another embodiment, anattachment member includes a fastener, such as a screw fastener. Inanother embodiment, an attachment member is formed of a magneticmaterial. In such a case, the module and bay may include magneticmaterials of opposite polarities so as to provide an attractive force tosecure the module to the bay. In another embodiment, the attachmentmember includes one or more tracks or rails in the bay. In such a case,a module includes one or more structures for mating with the one or moretracks or rails, thereby securing the module to the rack 709.Optionally, power may be provided by the rails.

An example of a structure that may permit a module to mate with a rackmay include one or more pins. In some cases, modules receive powerdirectly from the rack. In some cases, a module may be a power sourcelike a lithium ion, or fuel cell powered battery that powers the deviceinternally. In an example, the modules are configured to mate with therack with the aid of rails, and power for the modules comes directlyfrom the rails. In another example, the modules mate with the rack withthe aid of attachment members (rails, pins, hooks, fasteners), but poweris provided to the modules wirelessly, such as inductively (i.e.,inductive coupling). In some embodiments, a module mating with a rackneed not require pins. For example, an inductive electricalcommunication may be provided between the module and rack or othersupport. In some instances, wireless communications may be used, such aswith the aid of ZigBee communications or other communication protocolsor protocols that may be developed in the future.

Each module may be removable from the rack 709. In some situations, onemodule is replaceable with a like, similar or different module. In anembodiment, a module is removed from the rack 709 by sliding the moduleout of the rack. In another embodiment, a module is removed from therack 709 by twisting or turning the module such that an attachmentmember of the module disengages from the rack 709. Removing a modulefrom the rack 709 may terminate any electrical connectivity between themodule and the rack 709.

In an embodiment, a module is attached to the rack by sliding the moduleinto the bay. In another embodiment, a module is attached to the rack bytwisting or turning the module such that an attachment member of themodule engages the rack 709. Attaching a module to the rack 709 mayestablish an electrical connection between the module and the rack. Theelectrical connection may be for providing power to the module or to therack or to the device from the module and/or providing a communicationsbus between the module and one or more other modules or a controller ofthe system 700.

Each bay of the rack may be occupied or unoccupied. As illustrated, allbays of the rack 709 are occupied with a module. In some situations,however, one or more of the bays of the rack 709 are not occupied by amodule. In an example, the first module 701 has been removed from therack. The system 700 in such a case may operate without the removedmodule.

In some situations, a bay may be configured to accept a subset of thetypes of modules the system 700 is configured to use. For example, a baymay be configured to accept a module capable of running an agglutinationassay but not a cytometry assay. In such a case, the module may be“specialized” for agglutination. Agglutination may be measured in avariety of ways. Measuring the time-dependent change in turbidity of thesample is one method. One can achieve this by illuminating the samplewith light and measuring the reflected light at 90 degrees with anoptical sensor, such as a photodiode or camera. Over time, the measuredlight would increase as more light is scattered by the sample. Measuringthe time dependent change in transmittance is another example. In thelatter case, this can be achieved by illuminating the sample in a vesseland measuring the light that passes through the sample with an opticalsensor, such as a photodiode or a camera. Over time, as the sampleagglutinates, the measured light may reduce or increase (depending, forexample, on whether the agglutinated material remains in suspension orsettles out of suspension). In other situations, a bay may be configuredto accept all types of modules that the system 700 is configured to use,ranging from detection stations to the supporting electrical systems.

Each of the modules may be configured to function (or perform)independently from the other modules. In an example, the first module701 is configured to perform independently from the second 702, third703, fourth 704, fifth 705 and sixth 706 modules. In other situations, amodule is configured to perform with one or more other modules. In sucha case, the modules may enable parallel processing of one or moresamples. In an example, while the first module 701 prepares a sample,the second module 702 assays the same or different sample. This mayenable a minimization or elimination of downtime among the modules.

The support structure (or rack) 709 may have a server typeconfiguration. In some situations, various dimensions of the rack arestandardized. In an example, spacing between the modules 701-706 isstandardized as multiples of at least about 0.5 inches, or 1 inch, or 2inches, or 3 inches, or 4 inches, or 5 inches, or 6 inches, or 7 inches,or 8 inches, or 9 inches, or 10 inches, or 11 inches, or 12 inches.

The rack 709 may support the weight of one or more of the modules701-706. Additionally, the rack 709 has a center of gravity that isselected such that the module 701 (top) is mounted on the rack 709without generating a moment arm that may cause the rack 709 to spin orfall over. In some situations, the center of gravity of the rack 709 isdisposed between the vertical midpoint of the rack and a base of therack, the vertical midpoint being 50% from the base of the rack 709 anda top of the rack. In an embodiment, the center of gravity of the rack709, as measured along a vertical axis away from the base of the rack709, is disposed at least about 0.1%, or 1%, or 10%, or 20%, or 30%, or40%, or 50%, or 60%, or 70%, or 80%, or 90%, or 100% of the height ofthe rack as measured from the base of the rack 709.

A rack may have multiple bays (or mounting stations) configured toaccept one or more modules. In an example, the rack 709 has six mountingstations for permitting each of the modules 701-706 to mount the rack.In some situations, the bays are on the same side of the rack. In othersituations, the bays are on alternating sides of the rack.

In some embodiments, the system 700 includes an electrical connectivitycomponent for electrically connecting the modules 701-706 to oneanother. The electrical connectivity component may be a bus, such as asystem bus. In some situations, the electrical connectivity componentalso enables the modules 701-706 to communicate with each other and/or acontroller of the system 700.

In some embodiments, the system 700 includes a controller (not shown)for facilitating processing of samples with the aid of one or more ofthe modules 701-706. In an embodiment, the controller facilitatesparallel processing of the samples in the modules 701-706. In anexample, the controller directs the sample handling system 708 toprovide a sample in the first module 701 and second module 702 to rundifferent assays on the sample at the same time. In another example, thecontroller directs the sample handling system 708 to provide a sample inone of the modules 701-706 and also provide the sample (such as aportion of a finite volume of the sample) to the cytometry station 707so that cytometry and one or more other sample preparation proceduresand/or assays are done on the sample in parallel. In such fashion, thesystem minimizes, if not eliminates, downtime among the modules 701-706and the cytometry station 707.

Each individual module of the plurality of modules may include a samplehandling system for providing samples to and removing samples fromvarious processing and assaying modules of the individual module. Inaddition, each module may include various sample processing and/orassaying modules, in addition to other components for facilitatingprocessing and/or assaying of a sample with the aid of the module. Thesample handling system of each module may be separate from the samplehandling system 708 of the system 700. That is, the sample handlingsystem 708 transfers samples to and from the modules 701-706, whereasthe sample handling system of each module transfers samples to and fromvarious sample processing and/or assaying modules included within eachmodule.

In the illustrated example of FIG. 55C, the sixth module 706 includes asample handling system 710 including a suction-type pipette 711 andpositive displacement pipette 712. The sixth module 706 includes acentrifuge 713, a spectrophotometer 714, a nucleic acid assay (such as apolymerase chain reaction (PCR) assay) station 715 and PMT 716. Anexample of the spectrophotometer 714 is shown in FIG. 55C (see below).The sixth module 706 further includes a cartridge 717 for holding aplurality of tips for facilitating sample transfer to and from eachprocessing or assaying module of the sixth module.

In an embodiment, the suction type pipette 711 includes 1 or more, or 2or more, or 3 or more, or 4 or more, or 5 or more, or 6 or more, or 7 ormore, or 8 or more, or 9 or more, or 10 or more, or 15 or more, or 20 ormore, or 30 or more, or 40 or more, or 50 or more heads. In an example,the suction type pipette 711 is an 8-head pipette with eight heads. Thesuction type pipette 711 may be as described in other embodiments of theinvention.

In some embodiments, the positive displacement pipette 712 has acoefficient of variation less than or equal to about 20%, 15%, 12%, 10%,9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.3%, or 0.1% or less. Thecoefficient of variation is determined according to □ □ □, wherein ‘□’is the standard deviation and ‘□’ □ is the mean across samplemeasurements.

In an embodiment, all modules are identical to one another. In anotherembodiment, at least some of the modules are different from one another.In an example, the first, second, third, fourth, fifth, and sixthmodules 701-706 include a positive displacement pipette and suction-typepipette and various assays, such as a nucleic acid assay andspectrophotometer. In another example, at least one of the modules701-706 may have assays and/or sample preparation stations that aredifferent from the other modules. In an example, the first module 701includes an agglutination assay but not a nucleic acid amplificationassay, and the second module 702 includes a nucleic acid assay but notan agglutination assay. Modules may not include any assays.

In the illustrated example of FIG. 55C, the modules 701-706 include thesame assays and sample preparation (or manipulation) stations. However,in other embodiments, each module includes any number and combination ofassays and processing stations described herein.

The modules may be stacked vertically or horizontally with respect toone another. Two modules are oriented vertically in relation to oneanother if they are oriented along a plane that is parallel,substantially parallel, or nearly parallel to the gravitationalacceleration vector. Two modules are oriented horizontally in relationto one another if they are oriented along a plane orthogonal,substantially orthogonal, or nearly orthogonal to the gravitationalacceleration vector.

In an embodiment, the modules are stacked vertically, i.e., one moduleon top of another module. In the illustrated example of FIG. 55C, therack 709 is oriented such that the modules 701-706 are disposedvertically in relation to one another. However, in other situations themodules are disposed horizontally in relation to one another. In such acase, the rack 709 may be oriented such that the modules 701-706 may besituated horizontally alongside one another.

In yet another embodiment of a system 730 is shown with a plurality ofmodules 701 to 704. This embodiment shows a horizontal configurationwherein the modules 701 to 704 are mounted to a support structure 732 onwhich a transport device 734 can move along the X, Y, and/or optionallyZ axis to move elements such as but not limited sample vessels, tips,cuvettes, or the like within a module and/or between modules. By way ofnon-limiting example, the modules 701-704 are oriented horizontally inrelation to one another if they are oriented along a plane orthogonal,substantially orthogonal, or nearly orthogonal to the gravitationalacceleration vector.

It should be understood that, like the embodiment of FIG. 55C, modules701-704 may all be modules that are identical to one another. In anotherembodiment, at least some of the modules are different from one another.In an example, the first, second, third, and/or fourth modules 701-704may be replaced by one or more other modules that can occupy thelocation of the module being replaced. The other modules may optionallyprovide different functionality such as but not limited to a replacingone of the modules 701-704 with one or more cytometry modules 707,communications modules, storage modules, sample preparation modules,slide preparation modules, tissue preparation modules, or the like. Forexample, one of the modules 701-704 may be replaced with one or moremodules that provide a different hardware configuration such as but notlimited to provide a thermal controlled storage chamber for incubation,storage between testing, and/or storage after testing. Optionally, themodule replacing one or more of the modules 701-704 can provide anon-assay related functionality, such as but not limited to additionaltelecommunication equipment for the system 730, additional imaging oruser interface equipment, or additional power source such as but notlimited to batteries, fuel cells, or the like. Optionally, the modulereplacing one or more of the modules 701-704 may provide storage foradditional disposables and/or reagents or fluids. It should beunderstood that although some embodiments show only four modules mountedon the support structure, other embodiments having fewer or more modulesare not excluded from this horizontal mounting configuration. It shouldalso be understood that configurations may also be run with not everybay or slot occupied by a module, particularly in any scenario whereinone or more types of modules draw more power that other modules. In sucha configuration, power otherwise directed to an empty bay can be used bythe module that may draw more power than the others.

It should be understood that, like the embodiment of FIG. 55C, modules701-706 may all be modules that are identical to one another. In anotherembodiment, at least some of the modules are different from one another.In an example, the first, second, third, and/or fourth modules 701-706may be replaced by one or more other modules that can occupy thelocation of the module being replaced. The other modules may optionallyprovide different functionality such as but not limited to a replacingone of the modules 701-706 with one or more cytometry modules 707,communications modules, storage modules, sample preparation modules,slide preparation modules, tissue preparation modules, or the like.

It should be understood that although some embodiments show only sixmodules mounted on the support structure, other embodiments having feweror more modules are not excluded from this horizontal and verticalmounting configuration. It should also be understood that configurationsmay also be run with not every bay or slot occupied by a module,particularly in any scenario wherein one or more types of modules drawmore power that other modules. In such a configuration, power otherwisedirected to an empty bay can be used by the module that may draw morepower than the others.

Some embodiments may provide a system with a plurality of modules 701,702, 703, 704, 706, and 707. Such an embodiment may have an additionalmodule that can with one or more modules that provide a differenthardware configuration such as but not limited to provide a thermalcontrolled storage chamber for incubation, storage between testing, orstorage after testing. Optionally, the module replacing one or more ofthe modules 701-704 can provide a non-assay related functionality, suchas but not limited to additional telecommunication equipment for thesystem, additional imaging or user interface equipment, or additionalpower source such as but not limited to batteries, fuel cells, or thelike. Optionally, the module replacing one or more of the modules701-707 may provide storage for additional disposables and/or reagentsor fluids.

It should be understood that although FIG. 55C shows seven modulesmounted on the support structure, other embodiments having fewer or moremodules are not excluded from this mounting configuration. It shouldalso be understood that configurations may also be run with not everybay or slot occupied by a module, particularly in any scenario whereinone or more types of modules draw more power that other modules. In sucha configuration, power otherwise directed to an empty bay can be used bythe module that may draw more power than the others.

In some embodiments, the modules 701-706 are in communication with oneanother and/or a controller of the system 700 by way of a communicationsbus (“bus”), which may include electronic circuitry and components forfacilitating communication among the modules and/or the controller. Thecommunications bus includes a subsystem that transfers data between themodules and/or controller of the system 700. A bus may bring variouscomponents of the system 700 in communication with a central processingunit (CPU), memory (e.g., internal memory, system cache) and storagelocation (e.g., hard disk) of the system 700.

A communications bus may include parallel electrical wires with multipleconnections, or any physical arrangement that provides logicalfunctionality as a parallel electrical bus. A communications bus mayinclude both parallel and bit-serial connections, and can be wired ineither a multidrop (i.e., electrical parallel) or daisy chain topology,or connected by switched hubs. In an embodiment, a communications busmay be a first generation bus, second generation bus or third generationbus. The communications bus permits communication between each of themodules and other modules and/or the controller. In some situations, thecommunications bus enables communication among a plurality of systems,such as a plurality of systems similar or identical to the system 700.

The system 700 may include one or more of a serial bus, parallel bus, orself-repairable bus. A bus may include a master scheduler that controldata traffic, such as traffic to and from modules (e.g., modules701-706), controller, and/or other systems. A bus may include anexternal bus, which connects external devices and systems to a mainsystem board (e.g., motherboard), and an internal bus, which connectsinternal components of a system to the system board. An internal busconnects internal components to one or more central processing units(CPUs) and internal memory.

In some embodiments, the communication bus may be a wireless bus. Thecommunications bus may be a Firewire (IEEE 1394), USB (1.0, 2.0, 3.0, orothers), Thunderbolt, or other protocols (current or developed in thefuture).

In some embodiments, the system 700 includes one or more buses selectedfrom the group consisting of Media Bus, Computer Automated Measurementand Control (CAMAC) bus, industry standard architecture (ISA) bus, USBbus, Firewire, Thunderbolt, extended ISA (EISA) bus, low pin count bus,MBus, MicroChannel bus, Multibus, NuBus or IEEE 1196, OPTi local bus,peripheral component interconnect (PCI) bus, Parallel AdvancedTechnology Attachment (ATA) bus, Q-Bus, S-100 bus (or IEEE 696), SBus(or IEEE 1496), SS-50 bus, STEbus, STD bus (for STD-80 [8-bit] and STD32[16-132-bit]), Unibus, VESA local bus, VMEbus, PC/104 bus, PC/104 Plusbus, PC/104 Express bus, PCI-104 bus, PCIe-104 bus, 1-Wire bus,HyperTransport bus, Inter-Integrated Circuit (I2C) bus, PCI Express (orPCIe) bus, Serial ATA (SATA) bus, Serial Peripheral Interface bus, UNDObus, SMBus, 2-wire or 3-wire interface, self-repairable elasticinterface buses and variants and/or combinations thereof.

In some situations, the system 700 includes a Serial PeripheralInterface (SPI), which is an interface between one or moremicroprocessors and peripheral elements or I/O components (e.g., modules701-706) of the system 700. The SPI can be used to attach 2 or more, or3 or more, or 4 or more, or 5 or more, or 6 or more, or 7 or more, or 8or more, or 9 or more, or 10 or more or 50 or more or 100 or more SPIcompatible I/O components to a microprocessor or a plurality ofmicroprocessors. In other instances, the system 700 includes RS-485 orother standards.

In an embodiment, an SPI is provided having an SPI bridge having aparallel and/or series topology. Such a bridge allows selection of oneof many SPI components on an SPI I/O bus without the proliferation ofchip selects. This is accomplished by the application of appropriatecontrol signals, described below, to allow daisy chaining the device orchip selects for the devices on the SPI bus. It does however retainparallel data paths so that there is no Daisy Chaining of data to betransferred between SPI components and a microprocessor.

In some embodiments, an SPI bridge component is provided between amicroprocessor and a plurality of SPI I/O components which are connectedin a parallel and/or series (or serial) topology. The SPI bridgecomponent enables parallel SPI using MISO and MOSI lines and serial(daisy chain) local chip select connection to other slaves (CSL/). In anembodiment, SPI bridge components provided herein resolve any issuesassociated with multiple chip selects for multiple slaves. In anotherembodiment, SPI bridge components provided herein support four, eight,sixteen, thirty two, sixty four or more individual chip selects for fourSPI enabled devices (CS1/-CS4/). In another embodiment, SPI bridgecomponents provided herein enable four times cascading with externaladdress line setting (ADR0-ADR1). In some situations, SPI bridgecomponents provided herein provide the ability to control up to eight,sixteen, thirty two, sixty four or more general output bits for controlor data. SPI bridge components provided herein in some cases enable thecontrol of up to eight, sixteen, thirty two, sixty four or more generalinput bits for control or data, and may be used for deviceidentification to the master and/or diagnostics communication to themaster.

One embodiment may use an SPI bridge scheme having master andparallel-series SPI slave bridges, in accordance with an embodiment ofthe invention. The SPI bus is augmented by the addition of a local chipselect (CSL/), module select (MOD_SEL) and select data in (DIN_SEL) intoa SPI bridge to allow the addition of various system features, includingessential and non-essential system features, such as cascading ofmultiple slave devices, virtual daisy chaining of device chip selects tokeep the module-to-module signal count at an acceptable level, thesupport for module identification and diagnostics, and communication tonon-SPI elements on modules while maintaining compatibility withembedded SPI complaint slave components. FIG. 41B shows an example of anSPI bridge, in accordance with an embodiment of the invention. The SPIbridge includes internal SPI control logic, a control register (8 bit,as shown), and various input and output pins.

Each slave bridge is connected to a master (also “SPI master” and“master bridge” herein) in a parallel-series configuration. The MOSI pinof each slave bridge is connected to the MOSI pin of the master bridge,and the MOSI pins of the slave bridges are connected to one another.Similarly, the MISO pin of each slave bridge is connected to the MISOpin of the master bridge, and the MISO pins of the slave bridges areconnected to one another.

Each slave bridge may be a module (e.g., one of the modules 701-706 ofFIG. 55C) or a component in a module. In an example, the First SlaveBridge is the first module 701, the Second Slave Bridge is the secondmodule 702, and so on. In another example, the First Slave Bridge is acomponent of a module.

At least one non-limiting example may use a module component diagramwith interconnected module pins and various components of a masterbridge and slave bridge, in accordance with an embodiment of theinvention. Slave bridges may be connected to a master bridge, inaccordance with an embodiment of the invention. The MISO pin of eachslave bridge is in electrical communication with a MOSI pin of themaster bridge. The MOSI pin of each slave bridge is in electricalcommunication with a MISO pin of the master bridge. The DIN_SEL pin ofthe first slave bridge (left) is in electrical communication with theMOSI pin of the first slave bridge. The DOUT_SEL pin of the first slavebridge is in electrical communication with the DIN_SEL of the secondslave (right). Additional slave bridges may be connected as the secondslave by bringing the DIN_SEL pins of each additional slave bridge inelectrical communication with a DOUT_SEL pin of a previous slave bridge.In such fashion, the slave bridge are connected in a parallel-seriesconfiguration.

In some embodiments, CLK pulses directed to connected SPI-Bridgescapture the state of DIN_SEL Bits shifted into the Bridges at theassertion of the Module Select Line (MOD_SEL). The number of DIN_SELbits corresponds to the number of modules connected together on aparallel-series SPI-Link. In an example, if the two modules areconnected in a parallel-series configuration (e.g. RS486), the number ofDIN_SEL is equal to two.

In an embodiment, SPI-Bridges which latch a ‘1’ during the moduleselection sequence become the ‘selected module’ set to receive 8 bitcontrol word during a following element selection sequence. EachSPI-Bridge may access up to 4 cascaded SPI Slave devices. Additionally,each SPI-Bridge may have an 8-Bit GP Receive port and 8-Bit GP TransmitPort. An ‘element selection’ sequence writes an 8 bit word into the‘selected module’ SPI-Bridge control register to enable subsequenttransactions with specific SPI devices or to read or write data via theSPI-Bridge GPIO port.

In an embodiment, element selection takes place by assertion of thelocal chip select line (CSL/) then clocking the first byte of MOSItransferred data word into the control register. In some cases, theformat of the control register is CS4 CS3 CS2 CS1 AD1 AD0 R/W N. Inanother embodiment, the second byte is transmit or receive data. WhenCSL/ is de-asserted, the cycle is complete.

In an SPI transaction, following the element selection sequence,subsequent SPI slave data transactions commence. The SPI CS/ (which maybe referred to as SS/) is routed to one of 4 possible bridged devices,per the true state of either CS4, CS3, CS2 or CS1. Jumper bits AD0, AD1are compared to AD0, AD1 of the control register allow up to fourSPI-Bridges on a module.

One embodiment shows a device having a plurality of modules mounted on aSPI link of a communications bus of the device, in accordance with anembodiment of the invention. Three modules are illustrated, namelyModule 1, Module 2 and Module 3. Each module includes one or more SPIbridges for bringing various components of a module in electricalconnection with the SPI link, including a master controller (includingone or more CPU's) in electrical communication with the SPI link. Module1 includes a plurality of SPI slaves in electrical communication witheach of SPI Bridge 00, SPI Bridge 01, SPI Bridge 10 and SPI Bridge 11.In addition, each module includes a Receive Data controller, TransmitData controller and Module ID jumpers.

In other embodiments, the modules 701-706 are configured to communicatewith one another and/or one or more controllers of the system 700 withthe aid of a wireless communications bus (or interface). In an example,the modules 701-706 communicate with one another with the aid of awireless communications interface. In another example, one or more ofthe modules 701-706 communicate with a controller of the system 700 withthe aid of a wireless communications bus. In some cases, communicationamong the modules 701-706 and/or one or more controllers of the systemis solely by way of a wireless communications bus. This mayadvantageously preclude the need for wired interfaces in the bays foraccepting the modules 701-706. In other cases, the system 700 includes awired interface that works in conjunction with a wireless interface ofthe system 700.

Although the system 700, as illustrated, has a single rack, a system,such as the system 700, may have multiple racks. In some embodiments, asystem has at most 1, or 2, or 3, or 4, or 5, or 6, or 7, or 8, or 9, or10, or 20, or 30, or 40, or 50, or 100, or 1000, or 10,000 racks. In anembodiment, the system has a plurality of racks disposed in aside-by-side configuration.

In some embodiments, a user provides a sample to a system having one ormore modules, such as the system 700 of FIG. 55C. The user provides thesample to a sample collection module of the system. In an embodiment,the sample collection module includes one or more of a lancet, needle,microneedle, venous draw, scalpel, cup, swab, wash, bucket, basket, kit,permeable matrix, or any other sample collection mechanism or methoddescribed elsewhere herein. Next, the system directs the sample from thesample collection module to one or more processing modules (e.g.,modules 701-706) for sample preparation, assaying and/or detection. Inan embodiment, the sample is directed from the collection module to theone or more processing modules with the aid of a sample handling system,such as a pipette. Next, the sample is processed in the one or moremodules. In some situations, the sample is assayed in the one or moremodules and subsequently put through one or more detection routines.

In some embodiments, following processing in the one or more modules,the system communicates the results to a user or a system (e.g., server)in communication with the system. Other systems or users may then accessthe results to aid in treating or diagnosing a subject.

In an embodiment, the system is configured for two-way communicationwith other systems, such as similar or like systems (e.g., a rack, suchas that described in the context of FIG. 55C) or other computerssystems, including servers.

Devices and methods provided herein, by enabling parallel processing,may advantageously decrease the energy or carbon footprint of point ofservice systems. In some situations, systems, such as the system 700 ofFIG. 55C, has a footprint that is at most 10%, or 15%, or 20%, or 25%,or 30%, or 35%, or 40%, or 45%, or 50%, or 55%, or 60%, or 65%, or 70%,or 75%, or 80%, or 85%, or 90%, or 95%, or 99% that of other point ofservice systems.

In some embodiments, methods are provided for detecting analytes. In anembodiment, a processing routine includes detecting the presence orabsence of an analyte. The processing routine is facilitated with theaid of systems and devices provided herein. In some situations, analytesare associated with biological processes, physiological processes,environmental conditions, sample conditions, disorders, or stages ofdisorders, such as one or more of autoimmune disease, obesity,hypertension, diabetes, neuronal and/or muscular degenerative diseases,cardiac diseases, and endocrine diseases.

In some situations, a device processes one sample at a time. However,systems provided herein are configured for multiplexing sampleprocessing. In an embodiment, a device processes multiple samples at atime, or with overlapping times. In an example, a user provides a sampleto a device having a plurality of modules, such as the system 700 ofFIG. 55C. The device then processes the sample with the aid of one ormore modules of the device. In another example, a user provides multiplesamples to a device having a plurality of modules. The device thenprocesses the samples at the same time with the aid of the plurality ofmodules by processing a first sample in a first module while processinga second sample in second module.

The system may process the same type of sample or different types ofsamples. In an embodiment, the system processes one or more portions ofthe same sample at the same time. This may be useful if various assayingand/or detection protocols on the same sample are desired. In anotherembodiment, the system processes different types of samples at the sametime. In an example, the system processes a blood and urine sampleconcurrently in either different modules of the system or a singlemodule having processing stations for processing the blood and urinesamples.

In some embodiments, a method for processing a sample with the aid of apoint of service system, such as the system 700 of FIG. 55C, comprisesaccepting testing criteria or parameters and determining a test order orschedule based on the criteria. The testing criteria is accepted from auser, a system in communication with the point of service system, or aserver. The criteria are selectable based on a desired or predeterminedeffect, such as minimizing time, cost, component use, steps, and/orenergy. The point of service system processes the sample per the testorder or schedule. In some situations, a feedback loop (coupled withsensors) enables the point of service system to monitor the progress ofsample processing and maintain or alter the test order or schedule. Inan example, if the system detects that processing is taking longer thanthe predetermined amount of time set forth in the schedule, the systemspeeds up processing or adjusts any parallel processes, such as sampleprocessing in another module of the system. The feedback loop permitsreal-time or pseudo-real time (e.g., cached) monitoring. In somesituations, the feedback loop may provide permit reflex testing, whichmay cause subsequent tests, assays, preparation steps, and/or otherprocesses to be initiated after starting or completing another testand/or assay or sensing one or more parameter. Such subsequent tests,assays, preparation steps, and/or other processes may be initiatedautomatically without any human intervention. Optionally, reflex testingis performed in response to an assay result. Namely by way ofnon-limiting example, if a reflex test is ordered, a cartridge ispre-loaded with reagents for assay A and assay B. Assay A is the primarytest, and assay B is the reflexed test. If the result of assay A ismeets a predefined criteria initiating the reflex test, then assay B isrun with the same sample in the device. The device protocol is plannedto account for the possibility of running the reflex test. Some or allprotocol steps of assay B can be performed before the results for assayA are complete. For example, sample preparation can be completed inadvance on the device. It is possible also to run a reflex test with asecond sample from the patient. In some embodiments, devices and systemsprovided herein may contain components such that multiple differentassays and assay types may be reflex tested with the same device. Insome embodiments, multiple tests of clinical significance may beperformed in a single device provided herein as part of a reflex testingprotocol, where the performance of the same tests with known systems andmethods requires two or more separate devices. Accordingly, systems anddevices provided herein may permit, for example, reflex testing which isfaster and requires less sample than known systems and methods. Inaddition, in some embodiments, for reflex testing with a device providedherein, it is not necessary to know in advance which reflexed testedwill be performed.

In some embodiments, the point of service system may stick to apre-determined test order or schedule based on initial parameters and/ordesired effects. In other embodiments, the schedule and/or test ordermay be modified on the fly. The schedule and/or test order may bemodified based on one or more detected conditions, one or moreadditional processes to run, one or more processes to no longer run, oneor more processes to modify, one or more resource/component utilizationmodifications, one or more detected error or alert condition, one ormore unavailability of a resource and/or component, one or moresubsequent input or sample provided by a user, external data, or anyother reason.

In some examples, one or more additional samples may be provided to adevice after one or more initial samples are provided to the device. Theadditional samples may be from the same subject or different subjects.The additional samples may be the same type of sample as the initialsample or different types of samples (e.g., blood, tissue). Theadditional samples may be provided prior to, concurrently with, and/orsubsequent to processing the one or more initial samples on the device.The same and/or different tests or desired criteria may be provided forthe additional samples, as opposed to one another and/or the initialsamples. The additional samples may be processed in sequence and/or inparallel with the initial samples. The additional samples may use one ormore of the same components as the initial samples, or may use differentcomponents. The additional samples may or may not be requested in viewof one or more detected condition of the initial samples.

In some embodiments, the system accepts a sample with the aid of asample collection module, such as a lancet, scalpel, or fluid collectionvessel. The system then loads or accesses a protocol for performing oneor more processing routines from a plurality of potential processingroutines. In an example, the system loads a centrifugation protocol andcytometry protocol. In some embodiments, the protocol may be loaded froman external device to a sample processing device. Alternatively, theprotocol may already be on the sample processing device. The protocolmay be generated based on one or more desired criteria and/or processingroutines. In one example, generating a protocol may include generating alist of one or more subtasks for each of the input processes. In someembodiments, each subtask is to be performed by a single component ofthe one or more devices. Generating a protocol may also includegenerating the order of the list, the timing and/or allocating one ormore resources.

In an embodiment, a protocol provides processing details orspecifications that are specific to a sample or a component in thesample. For instance, a centrifugation protocol may include rotationalvelocity and processing time that is suited to a predetermined sampledensity, which enables density-dependent separation of a sample fromother material that may be present with a desirable component of thesample.

A protocol is included in the system, such as in a protocol repositoryof the system, or retrieved from another system, such as a database, incommunication with the system. In an embodiment, the system is inone-way communication with a database server that provides protocols tothe system upon request from the system for one or more processingprotocols. In another embodiment, the system is in two-way communicationwith a database server, which enables the system to upload user-specificprocessing routines to the database server for future use by the user orother users that may have use for the user-specific processing routines.

Referring now to FIGS. 56A and 56B, the transport container 4000 may beconfigured to contain therein a plurality of bodily fluid samples from aplurality of subjects such as patients. In some embodiments there aremultiple vessels of sample from each subject. Optionally, at least twoof the samples from the same subject have had different chemicalpre-treatment, such as but not limited to different anti-coagulant ineach vessel. Optionally, some embodiments may use a vessel that has twoor more separate chambers, wherein each chamber is configured to hold aportion of the fluid sample separate from fluid sample in anotherchamber. Some embodiments may include samples from a subject in singlechamber vessels and/or multi-chamber vessels.

As seen in FIGS. 56A and 56B, various views of one embodiment of thetransport container 4000 wherein the lid 4010 has a least a mesa portion4012 that is sized to fit into a recess 4020 on the bottom of thetransport container 4000 as seen in FIG. 57A so that the vessels 4000may be stackable. The transport container 4000 may have any of thefeatures described herein for other embodiments of transport containersdescribed herein.

FIG. 57B shows that there may be a tray 4030 in the transport container4000 that is fixed and/or removable from the transport container 4000.In one embodiment, the tray 4030 is held in place by a fixture devicesuch as but not limited to magnetic or metal portions 4032 that alignwith metal or magnetic portions in the chassis of the transportcontainer 4000 to form a magnetic connection. In some embodiments, thelength-to-width aspect ratio is in the range of about to 128:86 to127:85. Optionally, the length-to-width aspect ratio is in the range ofabout to 130:90 to 120:80. Optionally, the length of the tray is in therange of about to 130 mm to 120 mm and the width is in the range ofabout 90 mm to 80 mm. In some embodiments, the height or thickness ofthe tray is in the range of about 14 to 20 mm. The aspect ratio and/orsize is configured to hold a tray that is sized to fit a slot, recess,or other holder on a plate centrifuge. In this manner, the entire tray4030 can be centrifuged to prepare a plurality of the samples therein.

As seen in FIGS. 57B and 58B, the tray 4030 has a plurality of slots4034, wherein the slots 4034 are sized to hold at least one of thesample storage vessels. At least one portion 4040 of the slot 4034 has afirst shape and at least a second portion 4042 having a second shapedifferent from the first shape, wherein the shapes are keyed in a mannerthat the sample vessel can only be inserted into the slot 4034 in adesired orientation. As seen in FIG. 58B, one end is semi-circular whilethe other is asymmetrically shaped. The tray 4030 can also be shaped tohave cut outs 4036 or other shapes so that the tray 4030 can only beinserted in one orientation into the transport container 4000. It shouldalso be understood that the tray 4030 can be held in the tray so that auser cannot remove it using their fingers from the vessel 4000 withoutthe use of a tool or other tray extraction device. This minimizes therisk of user tampering. The tray 4030 can be configured to be held inthe transport container 4000 even when the transport container 4000 isupside down and can resist the pull of earth gravity.

FIGS. 59A and 59B show yet another embodiment wherein there a pluralityof slots 4100 in a tray 4102. The tray has a different aspect ratio(closer to square) and has a plurality of shaped slots in the tray tohold the sample vessels.

In at least one embodiment described herein, the process may optionallyinclude complete or substantially complete plasma separation of thesample at a sample collection location, such as but not limited to aremote location different from the analysis site, a patient servicecenter (PSC), or a retail site such as a pharmacy, such that the primaryseparation process of formed components from liquid component(s) allowsfor no more or minimal plasma being pushed out from a formed componentsuch as but not limited to the red blood cells through a separator gelbetween layers of the formed and liquid components at a later time, suchas during any second or subsequent separation step after the primaryseparation step.

In one embodiment, the period of time between the primary separationstep and the subsequent separation step is at least about 1 hour.Optionally, the period of time is at least about 2 hours. Optionally,the period of time is at least about 3 hours. Optionally, the period oftime is at least about 4 hours. Optionally, the period of time is atleast about 5 hours. Optionally, the period of time is at least about 6hours. Optionally, the period of time is at least about 7 hours.Optionally, the period of time is at least about 8 hours. Optionally,the period of time is at least about 9 hours. Optionally, the period oftime is at least about 10 hours. Optionally, the period of time is atleast about 11 hours. Optionally, the period of time is at least about12 hours. Optionally, the period of time is at least about 13 hours.Optionally, the period of time is at least about 14 hours. Optionally,the period of time is at least about 15 hours. Optionally, the period oftime is at least about 16 hours. Optionally, the period of time is atleast about 17 hours. Optionally, the period of time is at least about18 hours. Optionally, the period of time is at least about 19 hours.Optionally, the period of time is at least about 20 hours. Optionally,the period of time is at least about 21 hours. Optionally, the period oftime is at least about 22 hours. Optionally, the period of time is atleast about 23 hours. Optionally, the period of time is at least about24 hours. Optionally, the period of time is at least about 28 hours.Optionally, the period of time is at least about 32 hours. Optionally,the period of time is at least about 36 hours. Optionally, the period oftime is at least about 40 hours. Optionally, the period of time is atleast about 44 hours. Optionally, the period of time is at least about48 hours.

In one embodiment, the period of time is at least the time after primaryseparation that is sufficient for excess serum or plasma that has beenin contact with the red cells to form wherein such subsequent separationstep allows for the excess serum or plasma to be expressed fromunderneath a separation barrier such as but not limited to a gel barrierbetween formed components and most of the liquid component in thesample.

In one embodiment, the initial separation step comprises centrifugingfor at least about 3000 g. In one embodiment, the initial separationstep comprises centrifuging for at least about 3100 g. In oneembodiment, the initial separation step comprises centrifuging for atleast about 3200 g. In one embodiment, the initial separation stepcomprises centrifuging for at least about 3300 g. In one embodiment, theinitial separation step comprises centrifuging for at least about 3400g. In one embodiment, the initial separation step comprises centrifugingfor at least about 3500 g. Optionally, the method comprises a primarycentrifugation step of at least about 3550 g. Optionally, the methodcomprises a primary centrifugation step of at least about 3575 g.Optionally, the method comprises a primary accelerated sedimentationforce such as but not limited to a centrifugation step of at least about3700 g. Optionally, the method comprises a primary acceleratedsedimentation force such as but not limited to a centrifugation step ofat least about 3800 g. Optionally, the method comprises a primaryaccelerated sedimentation force such as but not limited to acentrifugation step of at least about 3900 g. Optionally, the methodcomprises a primary accelerated sedimentation force such as but notlimited to a centrifugation step of at least about 3950 g. In someembodiments, the g-force generated in the primary centrifugation stepherein may be no more than 3100 g, 3200 g, 3300 g, 3400 g, 3500 g, 3600g, 3700 g, 3800 g, 3900 g, or 3990 g. In some embodiments, the g-forcegenerated in the primary centrifugation step may have a force selectedfrom a range having a minimum value of about 3000 g, 3100 g, 3200 g,3300 g, 3400 g, 3500 g, 3600 g, 3700 g, 3800 g, 3900 g, or 3950 g, and amaximum value of 3100 g, 3200 g, 3300 g, 3400 g, 3500 g, 3600 g, 3700 g,3800 g, 3900 g, or 3990 g. In at least one embodiment, for any of theforegoing, the minimum force may be at least 1400 g. In at least oneembodiment, for any of the foregoing, the minimum force may be at least1500 g. In at least one embodiment, for any of the foregoing, theminimum force may be at least 1600 g. In at least one embodiment, forany of the foregoing, the minimum force may be at least 1700 g. In atleast one embodiment, for any of the foregoing, the minimum force may beat least 1800 g. In at least one embodiment, for any of the foregoing,the minimum force may be at least 1900 g. In at least one embodiment,for any of the foregoing, the minimum force may be at least 2000 g. Forat least the foregoing embodiments, “g” is in reference to theacceleration of gravity at sea level on Earth, which is about 9.8 m/s².

Optionally, the sample is centrifuged for at least about 1 minute.Optionally, the sample is centrifuged for at least about 2 minutes.Optionally, the sample is centrifuged for at least about 3 minutes.Optionally, the sample is centrifuged for at least about 4 minutes.Optionally, the sample is centrifuged for at least about 5 minutes.Optionally, the sample is centrifuged for at least about 6 minutes.Optionally, the sample is centrifuged for at least about 7 minutes.Optionally, the sample is centrifuged for at least about 8 minutes.Optionally, the sample is centrifuged for at least about 9 minutes.Optionally, the sample is centrifuged for at least about 10 minutes. Insome embodiments, the centrifugation in the primary centrifugation stepat the desired force or force range described in the previous paragraphmay be for a time period selected from a range having a minimum value of1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 6 minutes, 7minutes, 8 minutes, 9 minutes, or 10 minutes, and a maximum value of 2minutes, 3 minutes, 4 minutes, 5 minutes, 6 minutes, 7 minutes, 8minutes, 9 minutes, 10 minutes, or 11 minutes.

Optionally, the first or primary separation step to separate the plasmafrom the red blood cells occurs within 5 min of sample being collectedinto sample container(s). Optionally, the first or primary separationstep to separate the plasma from the red blood cells occurs within 10min of sample being collected into sample container(s). Optionally, thefirst or primary separation step to separate the plasma from the redblood cells occurs within 15 min of sample being collected into samplecontainer(s). Optionally, the first or primary separation step toseparate the plasma from the red blood cells occurs within 20 min ofsample being collected into sample container(s). Optionally, the firstor primary separation step to separate the plasma from the red bloodcells occurs nor more than about 5 minutes after the sample beingcollected into sample container(s). Optionally, the first or primaryseparation step to separate the plasma from the red blood cells occursnor more than about 10 minutes after the sample being collected intosample container(s). Optionally, the first or primary separation step toseparate the plasma from the red blood cells occurs nor more than about15 minutes after the sample being collected into sample container(s).Optionally, the first or primary separation step to separate the plasmafrom the red blood cells occurs nor more than about 20 minutes after thesample being collected into sample container(s).

Optionally, a secondary centrifugation step such as but not limited to acentrifugation spin for leveling the sample post-transport to areceiving location is performed. In one embodiment, the g-force of thissecondary or subsequent centrifugation is no more than about 43% of theg-force of the first centrifugation. In one embodiment, the g-force ofthis secondary or subsequent centrifugation is no more than about 40% ofthe g-force of the first centrifugation. In one embodiment, the g-forceof this secondary or subsequent centrifugation is no more than about 30%of the g-force of the first centrifugation. In one embodiment, theg-force of this secondary or subsequent centrifugation is no more thanabout 25% of the g-force of the first centrifugation. In one embodiment,the g-force of this secondary or subsequent centrifugation is no morethan about 20% of the g-force of the first centrifugation. In oneembodiment, the g-force of this secondary or subsequent centrifugationis no more than about 15% of the g-force of the first centrifugation. Inone embodiment, the g-force of this secondary or subsequentcentrifugation is no more than about 12.5% of the g-force of the firstcentrifugation. In one embodiment, the g-force of this secondary orsubsequent centrifugation is no more than about 10% of the g-force ofthe first centrifugation.

In one embodiment, the secondary or subsequent spin is no more than 1400g. Optionally, the secondary spin is no more than about 1300 g.Optionally, the secondary spin is no more than about 1200 g. Optionally,the secondary spin is no more than about 1100 g. Optionally, thesecondary spin is no more than about 1000 g. Optionally, the secondaryspin is no more than about 900 g. Optionally, the secondary spin is nomore than about 800 g. Optionally, the secondary spin is no more thanabout 700 g. Optionally, the secondary spin is no more than about 600 g.Optionally, the secondary spin is no more than about 500 g. Optionally,the secondary spin is no more than about 400 g. Optionally, thesecondary spin is no more than about 300 g. Optionally, the secondaryspin is no more than about 200 g. Optionally, the secondary spin is nomore than about 100 g. In at least one embodiment, for any of theforegoing, the minimum force may be at least 10 g. In at least oneembodiment, for any of the foregoing, the minimum force may be at least20 g. In at least one embodiment, for any of the foregoing, the minimumforce may be at least 30 g. In at least one embodiment, for any of theforegoing, the minimum force may be at least 40 g. In at least oneembodiment, for any of the foregoing, the minimum force may be at least50 g. By way of non-limiting example, in one embodiment, the secondaryspin is about 500 g or less but greater than at least 10 g. Optionally,in one embodiment, the secondary spin is about 500 g or less but greaterthan at least 20 g. Optionally, in one embodiment, the secondary spin isabout 500 g or less but greater than at least 30 g. Optionally, in oneembodiment, the secondary spin is about 500 g or less but greater thanat least 40 g. Optionally, in one embodiment, the secondary spin isabout 500 g or less but greater than at least 50 g. By way ofnon-limiting example, in one embodiment, the secondary spin is about 400g or less but greater than at least 10 g. Optionally, in one embodiment,the secondary spin is about 400 g or less but greater than at least 20g. Optionally, in one embodiment, the secondary spin is about 400 g orless but greater than at least 30 g. Optionally, in one embodiment, thesecondary spin is about 400 g or less but greater than at least 40 g.Optionally, in one embodiment, the secondary spin is about 400 g or lessbut greater than at least 50 g.

By way of non-limiting example, in one embodiment, the secondary spin isabout 500 g or less but greater than a minimum about sufficient tocreate a horizontal, substantially flattened meniscus for the sample inthe vessel. The upper bound may be selected so as not to overly compressany formed blood components during this second centrifuge, wherein toomuch force may cause rupture or leakage of internal cellular fluid ormaterial into plasma of the sample, which can alter results. A lowerbound may be selected so that a horizontal, substantially flattenedmeniscus is formed for the sample in the vessel. In one embodiment, whendealing with volumes of between about 10 to about 100 microliters, thissubstantially flat, non-angular surface can facilitate aspiration ofsample in an accurate and repeatable manner. In one embodiment, whendealing with volumes of between about 20 to about 150 microliters, thissubstantially flat, non-angular surface can facilitate aspiration ofsample in an accurate and repeatable manner. In one embodiment, whendealing with volumes of between about 30 to about 200 microliters, thissubstantially flat, non-angular surface can facilitate aspiration ofsample in an accurate and repeatable manner. A non-flat meniscus or oneat an angle to horizontal can create issues with partial aspiration.Optionally, the meniscus may be in a plane substantially perpendicularto a longitudinal axis of the vessel (such as horizontal plane which isperpendicular to a longitudinal axis of the vessel if the vessel is heldin a vertical orientation).

Optionally, the time period for the secondary centrifugation is aboutthe same as the first centrifugation. Optionally, the time period forthe secondary centrifugation is less than the time period of the firstcentrifugation. Optionally, the time period for the secondarycentrifugation is about 50% of the first centrifugation. Optionally, thetime period for the secondary centrifugation is about 40% of the firstcentrifugation. Optionally, the time period for the secondarycentrifugation is about 30% of the first centrifugation. Optionally, thetime period for the secondary centrifugation is about 20% of the firstcentrifugation. Optionally, the time period for the secondarycentrifugation is about 5% to about 50% of the first centrifugation.Optionally, the time period for the secondary centrifugation is about 5%to about 40% of the first centrifugation. Optionally, the time periodfor the secondary centrifugation is about 5% to about 33% of the firstcentrifugation. Optionally, the time period for the secondarycentrifugation is about 5% to about 30% of the first centrifugation.

Optionally, the force for the secondary centrifugation is about 5% toabout 30% of the first centrifugation and occurs after the sample hasbeen shipped from a first location to a second location. Optionally, theforce for the secondary centrifugation is about 5% to about 35% of thefirst centrifugation and occurs after the sample has been shipped from afirst location to a second location. Optionally, the force for thesecondary centrifugation is about 5% to about 40% of the firstcentrifugation and occurs after the sample has been shipped from a firstlocation to a second location. Optionally, the force for the secondarycentrifugation is about 5% to about 50% of the first centrifugation andoccurs after the sample has been shipped from a first location to asecond location.

Optionally, the force for the secondary centrifugation is about 5% toabout 50% of the first centrifugation and occurs after the sample hasbeen shipped from a first location to a second location, wherein thesecondary centrifugation does not exceed about 500 g. Optionally, theforce for the secondary centrifugation is about 5% to about 40% of thefirst centrifugation and occurs after the sample has been shipped from afirst location to a second location, wherein the secondarycentrifugation does not exceed about 500 g. Optionally, the force forthe secondary centrifugation is about 5% to about 30% of the firstcentrifugation and occurs after the sample has been shipped from a firstlocation to a second location, wherein the secondary centrifugation doesnot exceed about 500 g. Optionally, the force for the secondarycentrifugation is about 5% to about 20% of the first centrifugation andoccurs after the sample has been shipped from a first location to asecond location, wherein the secondary centrifugation does not exceedabout 500 g.

Optionally, the force for the secondary centrifugation is about 5% toabout 50% of the first centrifugation and occurs after the sample hasbeen shipped from a first location to a second location, wherein thesecondary centrifugation does not exceed about 400 g. Optionally, theforce for the secondary centrifugation is about 5% to about 40% of thefirst centrifugation and occurs after the sample has been shipped from afirst location to a second location, wherein the secondarycentrifugation does not exceed about 400 g. Optionally, the force forthe secondary centrifugation is about 5% to about 30% of the firstcentrifugation and occurs after the sample has been shipped from a firstlocation to a second location, wherein the secondary centrifugation doesnot exceed about 400 g. Optionally, the force for the secondarycentrifugation is about 5% to about 20% of the first centrifugation andoccurs after the sample has been shipped from a first location to asecond location, wherein the secondary centrifugation does not exceedabout 400 g.

Secondary spin post shipping of samples may be used for leveling thegel/plasma levels, getting plasma stuck on the cap and side walls of thesample container down (so there is no loss of sample), and moving andfibrin clots out of the plasma. This ensures optimal use of the sample(no losses), accurate imaging of the sample and sample volumecalculations, and effective aspiration of the sample from the samplecontainer.

Optionally, some embodiments may use a non-centrifugation second stepsuch as but not limited to a shaker, tapper, inverter, othernon-centrifugation mechanical method to urge sample on the cap therejoin other sample portions in the container, or any single or multiplecombination of the foregoing to move sample from the side wall or capinto the sample container.

In embodiments, a process provided herein may involve collection of ablood sample at a sample collection location and then shipping the bloodsample from the sample collection location to an analysis site which isat a different location than the sample collection location. Similarly,an analysis site may receive a blood sample which was collected at adifferent sample collection location. In such embodiments, the bloodsample or a portion thereof may be centrifuged at the sample collectionlocation and then centrifuged again at the analysis site, after arrivalof sample at the analysis site. In embodiments, the centrifugation ofthe blood sample at the sample collection site may facilitate theseparation of blood into i) plasma or serum and 2) formed components(e.g. red blood cells). In embodiments, there may be a gel-like materialprovided in a container for the blood, such that upon centrifugation ofthe blood in the container, the plasma or serum layer is separated fromthe formed components in the blood collection vessel by a gel layer. Inembodiments, the centrifugation of the blood sample at the analysis sitemay facilitate the movement of the blood sample in the container towardsthe bottom of the container (e.g. away from the cap or down the walls ofthe container).

In one embodiment, the period of time between the centrifugation of theblood sample at the sample collection site and the centrifugation at theanalysis site is at least about 1 hour. Optionally, the period of timeis at least about 2 hours. Optionally, the period of time is at leastabout 3 hours. Optionally, the period of time is at least about 4 hours.Optionally, the period of time is at least about 5 hours. Optionally,the period of time is at least about 6 hours. Optionally, the period oftime is at least about 7 hours. Optionally, the period of time is atleast about 8 hours. Optionally, the period of time is at least about 9hours. Optionally, the period of time is at least about 10 hours.Optionally, the period of time is at least about 11 hours. Optionally,the period of time is at least about 12 hours. Optionally, the period oftime is at least about 13 hours. Optionally, the period of time is atleast about 14 hours. Optionally, the period of time is at least about15 hours. Optionally, the period of time is at least about 16 hours.Optionally, the period of time is at least about 17 hours. Optionally,the period of time is at least about 18 hours. Optionally, the period oftime is at least about 19 hours. Optionally, the period of time is atleast about 20 hours. Optionally, the period of time is at least about21 hours. Optionally, the period of time is at least about 22 hours.Optionally, the period of time is at least about 23 hours. Optionally,the period of time is at least about 24 hours. Optionally, the period oftime is at least about 28 hours. Optionally, the period of time is atleast about 32 hours. Optionally, the period of time is at least about36 hours. Optionally, the period of time is at least about 40 hours.Optionally, the period of time is at least about 44 hours. Optionally,the period of time is at least about 48 hours.

In one embodiment, the centrifugation of the blood sample at the samplecollection site comprises centrifuging at least 3000 g. In oneembodiment, the centrifugation of the blood sample at the samplecollection site comprises centrifuging at least 3100 g. In oneembodiment, the centrifugation of the blood sample at the samplecollection site comprises centrifuging at least 3200 g. In oneembodiment, the centrifugation of the blood sample at the samplecollection site comprises centrifuging at least 3300 g. In oneembodiment, the centrifugation of the blood sample at the samplecollection site comprises centrifuging at least 3400 g. In oneembodiment, the centrifugation of the blood sample at the samplecollection site comprises centrifuging at least 3500 g. Optionally, thecentrifugation of the blood sample at the sample collection sitecomprises centrifuging at least 3550 g. Optionally, the centrifugationof the blood sample at the sample collection site comprises centrifugingat least 3575 g. Optionally, the centrifugation of the blood sample atthe sample collection site comprises centrifuging at least 3700 g.Optionally, the centrifugation of the blood sample at the samplecollection site comprises centrifuging at least 3800 g. Optionally, thecentrifugation of the blood sample at the sample collection sitecomprises centrifuging at least 3900 g. Optionally, the centrifugationof the blood sample at the sample collection site comprises centrifugingat least 3950 g. Optionally, the sample is centrifuged for at leastabout 1 minute. Optionally, the sample is centrifuged for at least about2 minutes. Optionally, the sample is centrifuged for at least about 3minutes. Optionally, the sample is centrifuged for at least about 4minutes. Optionally, the sample is centrifuged for at least about 5minutes. Optionally, the sample is centrifuged for at least about 6minutes. Optionally, the sample is centrifuged for at least about 7minutes. Optionally, the sample is centrifuged for at least about 8minutes. Optionally, the sample is centrifuged for at least about 9minutes. Optionally, the sample is centrifuged for at least about 10minutes.

Optionally, the g-force of the centrifugation at the analysis site is nomore than about 43% of the g-force of the centrifugation at the samplecollection site. Optionally, the g-force of the centrifugation at theanalysis site is no more than about 40% of the g-force of thecentrifugation at the sample collection site. Optionally, the g-force ofthe centrifugation at the analysis site is no more than about 30% of theg-force of the centrifugation at the sample collection site. Optionally,the g-force of the centrifugation at the analysis site is no more thanabout 25% of the g-force of the centrifugation at the sample collectionsite. Optionally, the g-force of the centrifugation at the analysis siteis no more than about 20% of the g-force of the centrifugation at thesample collection site. Optionally, the g-force of the centrifugation atthe analysis site is no more than about 15% of the g-force of thecentrifugation at the sample collection site. Optionally, the g-force ofthe centrifugation at the analysis site is no more than about 12.5% ofthe g-force of the centrifugation at the sample collection site.Optionally, the g-force of the centrifugation at the analysis site is nomore than about 10% of the g-force of the centrifugation at the samplecollection site.

In one embodiment, the centrifugation at the analysis site is no morethan 1400 g. In one embodiment, the centrifugation at the analysis siteis no more than 1300 g. In one embodiment, the centrifugation at theanalysis site is no more than 1200 g. In one embodiment, thecentrifugation at the analysis site is no more than 1100 g. In oneembodiment, the centrifugation at the analysis site is no more than 1000g. In one embodiment, the centrifugation at the analysis site is no morethan 900 g. In one embodiment, the centrifugation at the analysis siteis no more than 800 g. In one embodiment, the centrifugation at theanalysis site is no more than 700 g. In one embodiment, thecentrifugation at the analysis site is no more than 600 g. In oneembodiment, the centrifugation at the analysis site is no more than 500g. In one embodiment, the centrifugation at the analysis site is no morethan 400 g. In one embodiment, the centrifugation at the analysis siteis no more than 300 g.

Optionally, the time period for the centrifugation at the analysis siteis about the same as the centrifugation at the sample collection site.Optionally, the time period for the centrifugation at the analysis siteis less than the centrifugation at the sample collection site.Optionally, the time period for the centrifugation at the analysis siteis less than 50% of the centrifugation at the sample collection site.Optionally, the time period for the centrifugation at the analysis siteis less than 40% of the centrifugation at the sample collection site.Optionally, the time period for the centrifugation at the analysis siteis less than 30% of the centrifugation at the sample collection site.Optionally, the time period for the centrifugation at the analysis siteis less than 20% of the centrifugation at the sample collection site. Inat least some embodiments, a medical provider (or their staff whenappropriate) can be the sample collector, test result recipient, and/orboth. For example, in one embodiment, a healthcare professional such asbut not limited to a dentist can collect a sample as part of or separatefrom a dental procedure. Optionally, some embodiments may have thesample collected from suctioned blood and/or saliva from the subject'sdental procedure. The collected sample can be processed in the dentaloffice and/or shipped to a receiving location that receives a pluralityof samples for processing.

In embodiments, a bodily fluid sample used in a system, device, ormethod provided herein may be diluted. In embodiments, a bodily fluidsample may be diluted before it is transported from a first location toa second location. In embodiments, a bodily fluid sample may be dilutedafter it is transported from a first location to a second location. Inembodiments, a bodily fluid sample may be diluted both before and afterit is transported from a first location to a second location. Inembodiments, the bodily fluid sample may be diluted after it istransported from a first location to a second location and before it isused for performing one or more steps of a laboratory test at the secondlocation. An original bodily fluid sample may be diluted, for example,at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 50, 100, 200, 300, 400,500, 1000, 5,000, 10,000, 50,000, or 100,000-fold. As used herein, an“n-fold” dilution refers to a ratio by which an original sample isdiluted—e.g. an original sample which is diluted 5-fold contains, afterdilution, original sample at ⅕ of its original concentration (i.e. thediluted sample contains sample at ⅕ of the concentration of sample inthe original sample); similarly, an original sample which is diluted500-fold contains, after dilution, original sample at 1/500 of itsoriginal concentration. Thus, for example, if an original samplecontains 5 mg protein/microliter, and it is diluted 2-fold, the dilutedsample contains 2.5 mg protein/microliter. A bodily fluid sample may bedivided into any number of portions, and the various portions may bediluted to varying degrees of dilution, such that an original bodilyfluid sample may be processed to yield multiple diluted samples, eachhaving a different degree of dilution. Thus, for example, an originalbodily fluid sample may be divided into 5 portions, with one portionbeing diluted 8-fold, another portion being diluted 12-fold, anotherportion being diluted 3-fold, another portion being diluted 400-fold,and another portion being diluted 2,000-fold. Dilution of a sample maybe performed serially or in a single step. For a single-step dilution, aselected quantity of sample may be mixed with a selected quantity ofdiluent, in order to achieve a desired dilution of the sample. For aserial dilution, two or more separate sequential dilutions of the samplemay be performed in order to achieve a desired dilution of the sample.For example, a first dilution of the sample may be performed, and aportion of that first dilution may be used as the input material for asecond dilution, to yield a sample at a selected dilution level.

For dilutions described herein, an “original sample” or the like refersto the sample that is used at the start of a given dilution process.Thus, while an “original sample” may be a sample that is directlyobtained from a subject (e.g. whole blood), it may also include anyother sample (e.g. sample that has been processed or previously dilutedin a separate dilution procedure) that is used as the starting materialfor a given dilution procedure.

In some embodiments, a serial dilution of a sample may be performed asfollows. A selected quantity (e.g. volume) of an original sample may bemixed with a selected quantity of diluent, to yield a first dilutionsample. The first dilution sample (and any subsequent dilution samples)will have: i) a sample dilution factor (e.g. the amount by which theoriginal sample is diluted in the first dilution sample) and ii) aninitial quantity (e.g. the total quantity of the first dilution samplepresent after combining the selected quantity of original sample andselected quantity of diluent). For example, 10 microliters of anoriginal sample may be mixed with 40 microliters of diluent, to yield afirst dilution sample having a 5-fold sample dilution factor (ascompared with the original sample) and an initial quantity of 50microliters. Next, a selected quantity of the first dilution sample maybe mixed with a selected quantity of diluent, to yield a second dilutionsample. For example, 5 microliters of the first dilution sample may bemixed with 95 microliters of diluent, to yield a second dilution samplehaving an 100-fold dilution factor (as compared with the originalsample) and an initial quantity of 100 microliters. For each of theabove dilution steps, the original sample, dilution sample(s), anddiluent may be stored or mixed in fluidically isolated vessels.Sequential dilutions may continue in the preceding manner for as manysteps as needed to reach a selected sample dilution level/dilutionfactor. In embodiments, a sample may be diluted as described in, forexample, U.S. patent application Ser. No. 13/769,820, filed Feb. 18,2013, or any other document incorporated by reference elsewhere herein.

As used herein, a reagent that is, or may be used as, a “diluent” is onewhich is, e.g., useful for increasing the volume of a sample, or portionof a sample, or is useful for the preparation of a liquid formulation,such as a formulation reconstituted after lyophilization, or for addingto a sample, solution, or material for any other reason. In embodiments,a diluent may be buffered (e.g., to have a pH near pH 7, or near pH 7.4,or other desired pH), and may be pharmaceutically acceptable (safe andnon-toxic for administration to a human). A diluent typically does notreact with, or bind to, an analyte in a sample. Water may be a diluent,as may be an aqueous saline solution, a buffered solution, a solutioncontaining a surfactant, or any other solution. Exemplary diluentsinclude sterile water, bacteriostatic water for injection (BWFI), a pHbuffered solution (e.g. phosphate-buffered saline), sterile salinesolution, Ringer's solution or dextrose solution. In embodiments,diluents can include aqueous solutions of salts or buffers.

In embodiments, a bodily fluid sample or portion thereof which has been,for example, collected from a subject, processed, or transportedaccording to a system or method provided herein may be divided into atleast 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 50, 100, 200,300, 400, 500, 1000, 5,000, 10,000 or more different portions. Fordescriptions of division of a sample into multiple portions providedherein, an “original sample” or the like refers to the sample that isused at the start of a given sample division process. Thus, while an“original sample” may be, for example, a sample that was directlyobtained from a subject (e.g. whole blood), it may also include anyother sample (e.g. sample that has been processed or previously dividedin a separate sample division procedure) that is used as the startingmaterial for a given sample division procedure. In embodiments, an“original sample” may be subject to both sample division and dilutionsteps; in such circumstances, reference to the “original sample” refersto a starting material that is used for the combination sampledilution/sample division procedure. When a sample is divided intodifferent portions, the different portions may contain different amountsof the original sample. For instance, if an original sample having ofvolume of 100 microliters is divided into 5 portions, one portion maycontain 50 microliters original sample, another portion may contain 25microliters original sample, another portion may contain 15 microlitersoriginal sample, another portion may contain 8 microliters originalsample, and the last portion may contain 2 microliters original sample.Likewise, when a sample is both diluted and divided into differentportions, the different portions may have different degrees of dilutionrelative to the original sample. For example, if an original sample isdivided into three portions, one portion may be diluted 5-fold relativeto the original sample, another portion may be diluted 20-fold relativeto the original sample, and the third portion may be diluted 200-foldrelative to the original sample.

Thus, in an example, a bodily fluid sample may be collected from asubject at a first location (e.g. a sample collection site). The bodilyfluid sample as first collected from the subject may be considered an“original sample”. Such an “original sample” may be, for example, asmall quantity (e.g. less than 400, 300, 200, or 100 microliters) ofwhole blood from the subject. Shortly after or concurrent with thecollection of the “original sample” from the subject, the “originalsample” may be divided into at least a first portion and a secondportion, after which the first portion is transferred into a firstvessel and the second portion is transferred into a second vessel. Inembodiments, the first vessel may contain a first anticoagulant (e.g.EDTA) and the second vessel may contain a second anticoagulant (e.g.heparin). The first and second vessels may be transported according to asystem or method provided herein from the first location to a secondlocation. In embodiments, at the second location, the sample in one orboth of the vessels or portions thereof may be subject to furtherprocessing or analysis steps. For example, the sample in one or both ofthe vessels or portions thereof may be divided into additional portions,diluted, and/or used for performing one or more tests.

In another example, a bodily fluid sample may be shipped in a vesselfrom a first location to a second location according to systems andmethods provided herein. The bodily fluid sample in the vessel may bethe entirety of a sample that was collected from a subject, or a portionthereof. At the second location, at least some of the bodily fluidsample in the vessel may be removed from the vessel and used for asample division and/or dilution procedure. The sample that is removedfrom vessel and used for the sample division and/or dilution proceduremay be considered an “original sample”. That original sample may be, forexample, whole blood, plasma, serum, saliva, or urine, and mayconstitute the entirety of the sample that was transported in thevessel, or a portion thereof. That original sample may be divided intoany number of portions; the various portions may have different degreesof dilution relative to the original sample. For example, the originalsample removed from a transported vessel may have a volume of less thanor equal to 400, 300, 250, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30,25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 microliter. The originalsample removed from a transported vessel may then be divided into atleast 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 50, 100, 200,300, 400, 500, 1000, 5,000, 10,000 or more different portions. Inembodiments, the different portions may have different degrees ofdilution relative to the original sample. For example, the differentportions may have at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30,35, 40, 50, 100, 200, 300, 400, 500, 1000, or 5,000 different degrees ofdilution relative to the original sample, with the condition that thenumber of portions having different degrees of dilution does not exceedthe total number of portions prepared from the original sample. Thedifferent portions may have any type of dilution relative to theoriginal sample, including, for example, no dilution, at least 2-folddilution, at least 3-fold dilution, at least 5-fold dilution, at least10-fold dilution, at least 20-fold dilution, at least 50-fold dilution,at least 100-fold dilution, at least 500-fold dilution, at least1000-fold dilution, at least 5000-fold dilution, at least 10,000-folddilution, at least 50,000-fold dilution, or at least 100,000-folddilution. In embodiments, one or more different portions of an originalsample may be used for a laboratory test. In embodiments, one portion ofan original sample may be used for one laboratory test. A portion of anoriginal sample used for a laboratory test may be a diluted sample.

In embodiments, an original sample may be a whole blood sample obtainedfrom a subject. The original sample may be obtained from a subject'sdigit. The original sample may have a volume of no greater than 400,300, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 25, 20, 15, 10, 9, 8, 7,6, 5, 4, 3, 2, or 1 microliters. The original sample may be divided intomultiple portions. Division of the sample into multiple portions mayoccur before, after, or a combination of before and after the sample istransported from a first location to a second location according to asystem or method provided herein. In embodiments, the original samplemay be divided into at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30,35, 40, 50, 100, 200, 300, 400, 500, 1000, 5,000, 10,000 or moredifferent portions, and the different portions are used to perform atleast 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 50, 100, 200,300, 400, 500, 1000, 5,000, 10,000 different laboratory tests. Thedifferent portions of the original sample may have diluted originalsample. In embodiments, no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0.9,0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.05, or 0.01 microliter of theoriginal sample is used per each laboratory test.

In embodiments, an original sample may be plasma or serum obtained fromwhole blood sample obtained from a subject. The whole blood may beobtained from a subject's digit. The whole blood sample from which theplasma or serum is obtained may have a volume of no greater than 400,300, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 25, 20, 15, 10, 9, 8, 7,6, 5, 4, 3, 2, or 1 microliters. The plasma or serum original sample mayhave a volume of no greater than 300, 200, 150, 100, 90, 80, 70, 60, 50,40, 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 microliters. Theoriginal sample may be divided into multiple portions. Division of thesample into multiple portions may occur before, after, or a combinationof before and after the sample is transported from a first location to asecond location according to a system or method provided herein. Inembodiments, the original sample may be divided into at least 2, 3, 4,5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 50, 100, 200, 300, 400, 500,1000, 5,000, 10,000 or more different portions, and the differentportions are used to perform at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15,20, 25, 30, 35, 40, 50, 100, 200, 300, 400, 500, 1000, 5,000, 10,000different laboratory tests. The different portions of the originalsample may have diluted original sample.

In embodiments, the equivalent of no more than 10, 9, 8, 7, 6, 5, 4, 3,2, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.05, or 0.01microliter of an original sample is used for a laboratory test. Forexample, if an original sample is whole blood, and the original sampleis divided into multiple portions, and at least one of the portionscontains a diluted sample which contains original sample which has beendiluted 100-fold, and 5 microliters of that diluted sample is used toperform a laboratory test, then the equivalent of 0.05 microliters ofthe original sample (e.g. whole blood) is used for that test (5microliters×1/100 dilution). In another example, an original sample maybe whole blood. That whole blood may be processed to yield plasma [e.g.by separating the liquid components of the blood from the solidcomponents of blood (e.g. cells]. A certain volume of plasma may beobtained from a certain volume of whole blood—e.g. the volume of plasmathat may be obtained from a volume of whole blood may be, for example,at least or about 30%, 40%, 50%, 60%, or 70% of the volume of wholeblood. Thus, for example, if the volume of plasma from whole blood is50%, from 2 ml whole blood, 1 ml plasma may be obtained. The plasma fromwhole blood may be further diluted, and one or more diluted portions ofthe plasma may be used to perform one or more laboratory tests. Inanother example, an original sample may be whole blood. The whole bloodmay be processed to yield plasma, where the volume of plasma from thewhole blood is 60% of the whole blood (e.g. from 100 microliters wholeblood, 60 microliters plasma is obtained). The plasma may be diluted10-fold. 2 microliters of the diluted plasma may be used to perform alaboratory test. Thus, for that laboratory test, the equivalent of about0.33 microliters original sample (whole blood) is used to perform thetest (2 microliters×1/10 dilution×100/60 whole blood/plasma conversion).In another example, an original sample may be plasma, and the originalsample may be divided into multiple portions, and at least one of theportions contains a diluted sample which contains original sample whichhas been diluted 50-fold, and 4 microliters of that diluted sample isused to perform a laboratory test, then the equivalent of 0.08microliters of the original sample (e.g. plasma) is used for that test(4 microliters×1/50 dilution).

In embodiments, an original sample may be divided into at least 2, 3, 4,5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 50, 100, 200, 300, 400, 500,1000, 5,000, 10,000 or more different portions, and the differentportions may be used to perform at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15,20, 25, 30, 35, 40, 50, 100, 200, 300, 400, 500, 1000, 5,000, 10,000different laboratory tests. In some embodiments, at least as manyportions of sample are prepared as laboratory tests are performed withportions of a sample (e.g. in order to perform 10 laboratory tests withan original sample, the original sample may be divided into at least 10portions, with at least 1 portion being used per test). In certain otherembodiments, more than one laboratory test may be performed with asingle sample. For instance, in embodiments, an optical property of asample may be measured (e.g. cell count in a blood sample), and then thesame sample may be used to assay for an analyte in the blood. Thus, insome embodiments, more laboratory tests may be performed with anoriginal sample than the number of portions which are prepared from thesame original sample (e.g. 10 laboratory tests may be performed from anoriginal sample which is divided into only 8 portions).

When an original sample is divided into multiple portions, and themultiple portions are used to perform two or more laboratory tests, thelaboratory tests may be of the same type of laboratory test, or they maybe of different types of laboratory test. For instance, if an originalsample is divided into 10 portions, and the 10 portions are each usedfor a laboratory test, the laboratory test with each of the portions maybe an immunoassay. In another example, if an original sample is dividedinto 5 portions, and the 5 portions are each used for a laboratory test,the laboratory test with each of the portions may be a nucleic acidamplification-based test.

In other situations, when an original sample is divided into multipleportions, and the multiple portions are used to perform two or morelaboratory tests, at least two of the laboratory tests may be ofdifferent types of laboratory test. For instance, if an original sampleis divided into 5 portions, and the 5 portions are each used for alaboratory test, 2 of the portions may be used for an immunoassay (e.g.ELISA) and 3 of the portions may be used for a nucleic acidamplification-based test.

A bodily fluid sample or portion thereof transported according to asystem or method provided herein may be used in various types oflaboratory test, such as an immunoassay, nucleic acid amplificationassay, general chemistry assay, or cytometry assay. In embodiments, abodily fluid sample or portion thereof transported according to a systemor method provided herein may be used in any type of assay or laboratorytest as described in, for example, U.S. patent application Ser. No.13/769,820, filed Feb. 18, 2013, or any other document incorporated byreference elsewhere herein.

In some embodiments, a bodily fluid sample or portion thereoftransported according to a system or method provided herein may be usedin an immunoassay. As used herein, an “immunoassay” refers to any assaywhich involves probing for an analyte with an antibody which hasaffinity for the analyte. Immunoassays may include, for example,enzyme-linked immunosorbent (ELISA) assays and may include competitiveand non-competitive based-assays. The term “antibody” as used hereinrefers to immunoglobulin molecules and immunologically active portionsof immunoglobulin molecules, i.e., molecules that comprise anantigen-binding unit (“Abu” or plural “Abus”) which specifically binds(“immunoreacts with”) an antigen. Structurally, the simplest naturallyoccurring antibody (e.g., IgG) comprises four polypeptide chains, twoheavy (H) chains and two light (L) chains inter-connected by disulfidebonds. The immunoglobulins represent a large family of molecules thatinclude several types of molecules, such as IgD, IgG, IgA, IgM and IgE.The term “immunoglobulin molecule” includes, for example, hybridantibodies, or altered antibodies, and fragments thereof.Antigen-binding unit can be broadly divided into “single-chain” (“Sc”)and “non-single-chain” (“Nsc”) types based on their molecularstructures.

Also encompassed within the terms “antibodies” and “antigen-bindingunit” are immunoglobulin molecules and fragments thereof that may behuman, nonhuman (vertebrate or invertebrate derived), chimeric, orhumanized. For a description of the concepts of chimeric and humanizedantibodies see Clark et al., 2000 and references cited therein (Clark,(2000) Immunol. Today 21:397-402). In embodiments, “immunoassays” asprovided herein may also include assays in which the analyte to bemeasured in the assay is an antibody, and the antibody is probed forwith a molecule to which the antibody has affinity (e.g. a targetmolecule of the antibody).

In some embodiments, a bodily fluid sample or portion thereoftransported according to a system or method provided herein may be usedin a nucleic acid amplification assay. As used herein, a “nucleic acidamplification assay” refers to an assay in which the copy number of atarget nucleic acid may be increased. Nucleic acid amplification assaysmay include both isothermal and temperature-variable amplificationtechniques, and include, for example, techniques such as polymerasechain reaction (PCR) and loop-mediated isothermal amplification (LAMP).Typically, a nucleic acid amplification assay includes at least i) anucleic acid polymerase, ii) primers which can bind to a target nucleicacid sequence, and iii) free nucleotides which may be incorporated intosynthesized nucleic acid by a polymerase. Amplification of a targetnucleic acid may be detected in various ways, such as measuring thefluoresecence or turbidity of a reaction over a period of time.

In some embodiments, a bodily fluid sample or portion thereoftransported according to a system or method provided herein may be usedin a general chemistry assay. General chemistry assays may include, forexample, assays of a Basic Metabolic Panel [glucose, calcium, sodium(Na), potassium (K), chloride (Cl), CO2 (carbon dioxide, bicarbonate),creatinine, blood urea nitrogen (BUN)], assays of an Electrolyte Panel[sodium (Na), potassium (K), chloride (Cl), CO2 (carbon dioxide,bicarbonate)], assays of a Chem 14 Panel/Comprehensive Metabolic Panel[glucose, calcium, albumin, total protein, sodium (Na), potassium (K),chloride (Cl), CO2 (carbon dioxide, bicarbonate), creatinine, blood ureanitrogen (BUN), alkaline phosphatase (ALP), alanine aminotransferase(ALT/GPT), aspartate aminotransferase (AST/GOT), total bilirubin] assaysof a Lipid Profile/Lipid Panel [LDL cholesterol, HDL cholesterol, totalcholesterol, and triglycerides], assays of a Liver Panel/Liver Function[alkaline phosphatase (ALP), alanine aminotransferase (ALT/GPT),aspartate aminotransferase (AST/GOT), total bilirubin, albumin, totalprotein, gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH),prothrombin time (PT)], alkaline phosphatase (APase), hemoglobin, VLDLcholesterol, ethanol, lipase, pH, zinc protoporphyrin, direct bilirubin,blood typing (ABO, RHD), lead, phosphate, hemagglutination inhibition,magnesium, iron, iron uptake, fecal occult blood, and others,individually or in any combination.

In general chemistry assays provided herein, in some examples, the levelof an analyte in a sample is determined through one or more assay stepsinvolving a reaction of the analyte of interest with one or morereagents, leading to a detectable change in the reaction (e.g. change inthe turbidity of the reaction, generation of luminescence in thereaction, change in the color of the reaction, etc.). In some examples,a property of a sample is determined through one or more assay stepsinvolving a reaction of the sample of interest with one or morereagents, leading to a detectable change in the reaction (e.g. change inthe turbidity of the reaction, generation of luminescence in thereaction, change in the color of the reaction, etc.). Typically, as usedherein, “general chemistry” assays do not involve amplification ofnucleic acids, imaging of cells on a microscopy stage, or thedetermination of the level of an analyte in solution based on the use ofa labeled antibody/binder to determine the level of an analyte in asolution. In some embodiments, general chemistry assays are performedwith all reagents in a single vessel—i.e. to perform the reaction, allnecessary reagents are added to a reaction vessel, and during the courseof the assay, materials are not removed from the reaction or reactionvessel (e.g. there is no washing step; it is a “mix and read” reaction).General chemistry assays may also be, for example, colorimetric assays,enzymatic assays, spectroscopic assays, turbidimetric assays,agglutination assays, coagulation assays, and/or other types of assays.Many general chemistry assays may be analyzed by measuring theabsorbance of light at one or more selected wavelengths by the assayreaction (e.g. with a spectrophotometer). In some embodiments, generalchemistry assays may be analyzed by measuring the turbidity of areaction (e.g. with a spectrophotometer). In some embodiments, generalchemistry assays may be analyzed by measuring the chemiluminescencegenerated in the reaction (e.g. with a PMT, photodiode, or other opticalsensor). In some embodiments, general chemistry assays may be performedby calculations, based on experimental values determined for one or moreother analytes in the same or a related assay. In some embodiments,general chemistry assays may be analyzed by measuring fluorescence of areaction (e.g. with a detection unit containing or connected to i) alight source of a particular wavelength(s) (“excitation wavelength(s)”);and ii) a sensor configured to detect light emitted at a particularwavelength(s) (“emission wavelength(s)”). In some embodiments, generalchemistry assays may be analyzed by measuring agglutination in areaction (e.g. by measuring the turbidity of the reaction with aspectrophotometer or by obtaining an image of the reaction with anoptical sensor). In some embodiments, general chemistry assays may beanalyzed by imaging the reaction at one or more time points (e.g. with aCCD or CMOS optical sensor), followed by image analysis. Optionally,analysis may involve prothrombin time, activated partial thromboplastintime (APTT), either of which may be measured through a method such asbut not limited to turbidimetry. In some embodiments, general chemistryassays may be analyzed by measuring the viscosity of the reaction (e.g.with a spectrophotometer, where an increase in viscosity of the reactionchanges the optical properties of the reaction). In some embodiments,general chemistry assays may be analyzed by measuring complex formationbetween two non-antibody reagents (e.g. a metal ion to a chromophore;such a reaction may be measured with a spectrophotometer or throughcolorimetry using another device). In some embodiments, generalchemistry assays may be analyzed by non-ELISA or cytometry-based methodsfor assaying cellular antigens (e.g. hemagglutination assay for bloodtype, which may be measured, for example, by turbidity of the reaction).In some embodiments, general chemistry assays may be analyzed with theaid of electrochemical sensors (e.g. for carbon dioxide or oxygen).Additional methods may also be used to analyze general chemistry assays.

In some embodiments, a spectrophotometer may be used to measure ageneral chemistry assay. In some embodiments, general chemistry assaysmay be measured at the end of the assay (an “end-point” assay) or at twoor more times during the course of the assay (a “time-course” or“kinetic” assay).

In some embodiments, a bodily fluid sample or portion thereoftransported according to a system or method provided herein may be usedin a cytometry assay. Cytometry assays are typically used to optically,electrically, or acoustically measure characteristics of individualcells. For the purposes of this disclosure, “cells” may encompassnon-cellular samples that are generally of similar sizes to individualcells, including but not limited to vesicles (such as liposomes), smallgroups of cells, virions, bacteria, protozoa, crystals, bodies formed byaggregation of lipids and/or proteins, and substances bound to smallparticles such as beads or microspheres. Such characteristics includebut are not limited to size; shape; granularity; light scatteringpattern (or optical indicatrix); whether the cell membrane is intact;concentration, morphology and spatio-temporal distribution of internalcell contents, including but not limited to protein content, proteinmodifications, nucleic acid content, nucleic acid modifications,organelle content, nucleus structure, nucleus content, internal cellstructure, contents of internal vesicles (including pH), ionconcentrations, and presence of other small molecules such as steroidsor drugs; and cell surface (both cellular membrane and cell wall)markers including proteins, lipids, carbohydrates, and modificationsthereof. By using appropriate dyes, stains, or other labeling moleculeseither in pure form, conjugated with other molecules or immobilized in,or bound to nano- or micro-particles, cytometry may be used to determinethe presence, quantity, and/or modifications of specific proteins,nucleic acids, lipids, carbohydrates, or other molecules. Cytometricanalysis may, for example, be by flow cytometry or by microscopy. Flowcytometry typically uses a mobile liquid medium that sequentiallycarries individual cells to an optical, electrical or acoustic detector.Microscopy typically uses optical or acoustic means to detect stationarycells, generally by recording at least one magnified image. Inembodiments, a cytometry assay may involve obtaining images of one ormore cells in a sample. In embodiments, a sample may be provided on orin a microscope slide or cuvette, which may permit cells in a sample tosettle in a desired configuration for imaging. Images of cells may beobtained, for example, with a CCD or CMOS-based camera.

In some embodiments, laboratory test types may be classified based onhow the results of the test are detected. Different types of laboratorytest result detection may include, for example, i) luminescencedetection; ii) fluorescence detection; iii) absorbance detection; iv)light scattering detection; and v) imaging. Each of these detectionmethods are described, for example, in U.S. patent application Ser. No.13/769,820, filed Feb. 18, 2013, which is hereby incorporated in itsentirety for all purposes. Briefly, luminescence may be detected fromtests which yield a measurable light signal. Such reactions may be, forexample, chemiluminescent reactions. In order to detect the result of aluminescent reaction, a light detector such as a PMT or photodiode maybe used to detect light from an assay unit containing a luminescentreaction. Fluorescence may be detected, for example, with an optical setup which includes a light source and a light detector. The light sourcemay emit light of a particular wavelength(s). An assay unit containingthe test material may be situated in the path of the light source, suchthat light of the particular wavelength(s) reaches the contents of theassay unit (“excitation wavelength(s)”). The assay unit may contain amolecule of interest which, at least under some circumstances, absorbslight at the particular wavelength(s) from the light source, and,subsequently, releases light of a different wavelength. The lightdetector may be configured to detect light released by the molecule ofinterest (“emission wavelength(s)”). The light source and/or lightdetector may include a band-pass filter after the light source or beforethe light detector, in order to restrict the wavelength(s) of light fromthe light source or reaching the light detector. The light source maybe, for example, a light bulb, a laser or an LED, and the light detectormay be, for example, a PMT or photodiode. Absorbance may be detected,for example, with an optical set up which includes a light source and alight detector. The light source and light detector may be situated inline with each other, and configured such that an assay unit containingthe test material may be situated between the light source and lightdetector, such that some light may pass through the test material to thelight detector and some light may be absorbed. Different amounts oflight may be absorbed by the test material, based on the outcome of thetest. Similarly, transmission of light through the test material may bedetermined. For an absorbance/transmission determination assay, thewavelength(s) of light emitted by the light source may be same as thewavelength(s) of light detected by the light detector. The light sourcemay be, for example, a light bulb, a laser or an LED, and the lightdetector may be, for example, a PMT or photodiode. Light scattering maybe detected, for example, with an optical set up which includes a lightsource and a light detector. The light source and light detector may besituated at an angle relative to each other, and configured such that anassay unit containing the test material may be situated in line withboth the light source and light detector, such that light from the lightsource may reach the assay unit and be scattered by test material in theassay unit, to reach the light detector. Different amounts of light maybe scattered by the test material, based on the outcome of the test. Thelight source may be, for example, a light bulb, a laser or an LED, andthe light detector may be, for example, a PMT or photodiode. Images of atest material may be obtained, for example, by a detector which includesan image sensor (e.g. a CCD or CMOS sensor). Typically the image sensorwill be included in a camera. Images of test material may be analyzed,for example, by automated or manual image analysis, in order todetermine test results. Bodily fluid samples as provided herein may alsobe used in laboratory tests which detect results through non-opticalbased detection methods (e.g. measurements of conductivity,radioactivity, or temperature).

In embodiments, in order to perform an assay/test with a portion of abodily fluid sample, the portion of the bodily fluid sample may betransferred into an assay unit for at least one step of the assay/test.Assay units may have various form factors, such as a pipette tip, atube, or a microscope slide. Steps of an assay that may occur in anassay unit may include, for example, an analyte in the sample binding toa binder (e.g. an antibody) for the analyte, a target nucleic acid inthe sample being amplified in a nucleic acid amplification reaction, asample coagulating based on the addition of one or more reagents to thesample, or a sample adopting a configuration for optical analysis (e.g.cells settling on a surface of a microscope slide in order to facilitateobtaining one or more images of the cells). As used herein, the terms“assay” and “test” may be used interchangeably, unless the contextclearly dictates otherwise.

EXAMPLES

The following examples are offered for illustrative purposes only, andare not intended to limit the present disclosure in any way.

Example 1

A whole blood sample was obtained from a subject. The whole blood samplewas centrifuged in a vessel, in order to separate the whole blood intopelleted cells and a plasma supernatant. The centrifuged vessel wasmoved to an argon-purged glove box. Plasma was aspirated from thecentrifuged vessel and then aliquoted into 5 separate sample vessels asprovided herein, wherein the sample vessels each had an interior volumeof no greater than 100 microliters, wherein no greater than 95microliters plasma was aliquoted into each sample vessel, and whereineach of the sample vessels was of the same size and received the samevolume of plasma. The vessels each had a removable butyl rubber cap. The5 sample vessels were associated with the labels “0 hour”, “1 hour”, “2hours”, “8 hours”, and “24 hours”. At the respective time periodassociated with each sample vessel, the sample in each vessel wasassayed for bicarbonate. The results of the assays are provided below inTable 1.

TABLE 1 Time (hours) 0 1 2 8 24 Concentration 32.7 30.4 29.8 31.6 31.1Bicarbonate (mM)

As shown in Table 1, the bicarbonate in the sample was stable for atleast 24 hours in a sample vessel provided herein.

Example 2

A whole blood sample was obtained from a subject. EDTA was mixed withthe whole blood sample. Eighty microliters of the EDTA-containing bloodwas aliquoted into each of 10 sample vessels as provided herein, whereineach sample vessel had an interior volume of no greater than 100microliters, and was of the same size. The sample vessels wereassociated with labeled for analysis as follows: Real-time: Day 1, 2, 3,4, 5, and 7; Pre-centrifuged: Day 1, 2, 4, and 7. Each of the“pre-centrifuged” vessels were centrifuged at the time of aliquoting thesample into the vessel, to generate plasma and pelleted cells. Each ofthe “real-time” vessels was centrifuged on the respective day, togenerate plasma and pelleted cells. After sample was aliquoted into eachsample vessel, it was capped. On the respective day for each vessel,plasma was removed from the vessel and assayed for blood nitrogen urea(BUN). The BUN assay results are shown in the graph in FIG. 48. As shownin the graph, BUN remains stable in a sample in a sample vessel providedherein for at least 7 days, in both whole blood and plasma samples.

The publications discussed or cited herein are provided solely for theirdisclosure prior to the filing date of the present application. Nothingherein is to be construed as an admission that the present invention isnot entitled to antedate such publication by virtue of prior invention.Further, the dates of publication provided may be different from theactual publication dates which may need to be independently confirmed.All publications mentioned herein are incorporated herein by referenceto disclose and describe the structures and/or methods in connectionwith which the publications are cited. The following applications arefully incorporated herein by reference for all purposes: in U.S.Provisional Patent Application No. 61/435,250, filed Jan. 21, 2011(“SYSTEMS AND METHODS FOR SAMPLE USE MAXIMIZATION”), and U.S. PatentPublication No. 2009/0088336 (“MODULAR POINT-OF-CARE DEVICES, SYSTEMS,AND USES THEREOF”). The following applications are also fullyincorporated herein by reference for all purposes: U.S. PatentPublication 2005/0100937, U.S. Pat. No. 8,380,541; U.S. Pat. App. Ser.No. 61/766,113, filed Feb. 18, 2013; U.S. patent application Ser. No.13/769,798, filed Feb. 18, 2013; U.S. patent application Ser. No.13/769,779, filed Feb. 18, 2013; U.S. patent application Ser. No.13/769,820, filed Feb. 18, 2013; U.S. patent application Ser. No.13/244,947 filed Sep. 26, 2011; PCT/US2012/57155, filed Sep. 25, 2012;U.S. application Ser. No. 13/244,946, filed Sep. 26, 2011; U.S. patentapplication Ser. No. 13/244,949, filed Sep. 26, 2011; and U.S.Application Ser. No. 61/673,245, filed Sep. 26, 2011, the disclosures ofwhich patents and patent applications are all hereby incorporated byreference in their entireties. Furthermore, U.S. Patent Application Ser.No. 62/195,287 filed Jul. 21, 2015, U.S. Patent Application Ser. No.62/011,023 filed Jun. 11, 2014, U.S. patent application Ser. No.14/447,099 filed Jul. 30, 2014, U.S. patent application Ser. No.14/446,080 filed Jul. 29, 2014, and U.S. patent application Ser. No.14/098,177 filed Dec. 5, 2013 are all fully incorporated herein in theirentireties by reference for all purposes.

EMBODIMENTS

In one embodiment described herein, a device for collecting a bodilyfluid sample from a subject is provided comprising: at least two samplecollection pathways configured to draw the bodily fluid sample into thedevice from a single end of the device in contact with the subject,thereby separating the fluid sample into two separate samples; a secondportion comprising a plurality of sample vessels for receiving thebodily fluid sample collected in the sample collection pathways, thesample vessels operably engagable to be in fluid communication with thesample collection pathways, whereupon when fluid communication isestablished, the vessels provide a motive force to move a majority ofthe two separate samples from the pathways into the vessels.

In another embodiment described herein, a device for collecting a bodilyfluid sample is provided comprising: a first portion comprising at leastone fluid collection location leading to at least two sample collectionpathways configured to draw the fluid sample therein via a first type ofmotive force; a second portion comprising a plurality of sample vesselsfor receiving the bodily fluid sample collected in the sample collectionpathways, the sample vessels operably engagable to be in fluidcommunication with the sample collection pathways, whereupon when fluidcommunication is established, the vessels provide a second motive forcedifferent from the first motive force to move a majority of the bodilyfluid sample from the pathways into the vessels; wherein at least one ofthe sample collection pathways comprises a fill indicator to indicatewhen a minimum fill level has been reached and that at least one of thesample vessels can be engaged to be in fluid communication with at leastone of the sample collection pathways.

In another embodiment described herein, a device for collecting a bodilyfluid sample is provided comprising a first portion comprising at leasttwo sample collection channels configured to draw the fluid sample intothe sample collection channels via a first type of motive force, whereinone of the sample collection channels has an interior coating designedto mix with the fluid sample and another of the sample collectionchannels has another interior coating chemically different from saidinterior coating; a second portion comprising a plurality of samplevessels for receiving the bodily fluid sample collected in the samplecollection channels, the sample vessels operably engagable to be influid communication with the collection channels, whereupon when fluidcommunication is established, the vessels provide a second motive forcedifferent from the first motive force to move a majority of the bodilyfluid sample from the channels into the vessels; wherein vessels arearranged such that mixing of the fluid sample between the vessels doesnot occur.

In another embodiment described herein, a device for collecting a bodilyfluid sample is provided comprising: a first portion comprising aplurality of sample collection channels, wherein at least two of thechannels are configured to simultaneously draw the fluid sample intoeach of the at least two sample collection channels via a first type ofmotive force; a second portion comprising a plurality of sample vesselsfor receiving the bodily fluid sample collected in the sample collectionchannels, wherein the sample vessels have a first condition where thesample vessels are not in fluid communication with the sample collectionchannels, and a second condition where the sample vessels are operablyengagable to be in fluid communication with the collection channels,whereupon when fluid communication is established, the vessels provide asecond motive force different from the first motive force to move bodilyfluid sample from the channels into the vessels.

In another embodiment described herein, a sample collection device isprovided comprising: (a) a collection channel comprising a first openingand a second opening, and being configured to draw a bodily fluid samplevia capillary action from the first opening towards the second opening;and (b) a sample vessel for receiving the bodily fluid sample, thevessel being engagable with the collection channel, having an interiorwith a vacuum therein, and having a cap configured to receive a channel;wherein the second opening is defined by a portion the collectionchannel configured to penetrate the cap of the sample vessel, and toprovide a fluid flow path between the collection channel and the samplevessel, and the sample vessel has an interior volume no greater than tentimes larger than the interior volume of the collection channel.

In another embodiment described herein, a sample collection device isprovided comprising: (a) a collection channel comprising a first openingand a second opening, and being configured to draw a bodily fluid samplevia capillary action from the first opening towards the second opening;(b) a sample vessel for receiving the bodily fluid sample, the vesselbeing engagable with the collection channel, having an interior with avacuum therein, and having a cap configured to receive a channel; and(c) an adaptor channel configured to provide a fluid flow path betweenthe collection channel and the sample vessel, having a first opening anda second opening, the first opening being configured to contact thesecond opening of the collection channel, the second opening beingconfigured to penetrate the cap of the sample vessel.

In another embodiment described herein, a sample collection device isprovided comprising: (a) a body, containing a collection channel, thecollection channel comprising a first opening and a second opening, andbeing configured to draw a bodily fluid via capillary action from thefirst opening towards the second opening; (b) a base, containing asample vessel for receiving the bodily fluid sample, the sample vesselbeing engagable with the collection channel, having an interior with avacuum therein, and having a cap configured to receive a channel; and(c) a support, wherein, the body and the base are connected to oppositeends of the support, and are configured to be movable relative to eachother, such that sample collection device is configured to have anextended state and a compressed state, wherein at least a portion of thebase is closer to the body in the extended state of the device than inthe compressed state, the second opening of the collection channel isconfigured to penetrate the cap of the sample vessel, in the extendedstate of the device, the second opening of the collection channel is notin contact with the interior of the sample vessel, and in the compressedstate of the device, the second opening of the collection channelextends into the interior of the sample vessel through the cap of thevessel, thereby providing fluidic communication between the collectionchannel and the sample vessel.

In another embodiment described herein, a sample collection device isprovided comprising: (a) a body, containing a collection channel, thecollection channel comprising a first opening and a second opening, andbeing configured to draw a bodily fluid via capillary action from thefirst opening towards the second opening; (b) a base, containing asample vessel for receiving the bodily fluid sample, the sample vesselbeing engagable with the collection channel, having an interior with avacuum therein and having a cap configured to receive a channel; (c) asupport, and (d) an adaptor channel, having a first opening and a secondopening, the first opening being configured to contact the secondopening of the collection channel, and the second opening beingconfigured to penetrate the cap of the sample vessel, wherein, the bodyand the base are connected to opposite ends of the support, and areconfigured to be movable relative to each other, such that samplecollection device is configured to have an extended state and acompressed state, wherein at least a portion of the base is closer tothe body in the extended state of the device than in the compressedstate, in the extended state of the device, the adaptor channel is notin contact with one or both of the collection channel and the interiorof the sample vessel, and in the compressed state of the device, thefirst opening of the adaptor channel is in contact with the secondopening of the collection channel, and the second opening of the adaptorchannel extends into the interior of the sample vessel through the capof the vessel, thereby providing fluidic communication between thecollection channel and the sample vessel.

In another embodiment described herein, a device for collecting a fluidsample from a subject is provided comprising: (a) a body containing acollection channel, the collection channel comprising a first openingand a second opening, and being configured to draw a bodily fluid viacapillary action from the first opening towards the second opening; (b)a base, engagable with the body, wherein the base supports a samplevessel, the vessel being engagable with the collection channel, havingan interior with a vacuum therein, and having a cap configured toreceive a channel; wherein the second opening of the collection channelis configured to penetrate the cap of the sample vessel, and to providea fluid flow path between the collection channel and the sample vessel.

In another embodiment described herein, a device for collecting a fluidsample from a subject is provided comprising: (a) a body containing acollection channel, the collection channel comprising a first openingand a second opening, and being configured to draw a bodily fluid viacapillary action from the first opening towards the second opening; (b)a base, engagable with the body, wherein the base supports a samplevessel, the sample vessel being engagable with the collection channel,having an interior with a vacuum therein and having a cap configured toreceive a channel; and (c) an adaptor channel, having a first openingand a second opening, the first opening being configured to contact thesecond opening of the collection channel, and the second opening beingconfigured to penetrate the cap of the sample vessel.

It should be understood that one or more of the following features maybe adapted for use with any of the embodiments described herein. By wayof non-limiting example, the body may comprise of two collectionchannels. Optionally, the interior of the collection channel(s) arecoated with an anticoagulant. Optionally, the body comprises a firstcollection channel and a second collection channel, and the interior ofthe first collection channel is coated with a different anticoagulantthan the interior of the second collection channel. Optionally, thefirst anticoagulant is ethylenediaminetetraacetic acid (EDTA) and thesecond anticoagulant is different from EDTA. Optionally, the firstanticoagulant is citrate and the second anticoagulant is different fromcitrate. Optionally, the first anticoagulant is heparin and the secondanticoagulant is different from heparin. Optionally, one anticoagulantis heparin and the second anticoagulant is EDTA. Optionally, oneanticoagulant is heparin and the second anticoagulant is citrate.Optionally, one anticoagulant is citrate and the second anticoagulant isEDTA. Optionally, the body is formed from an optically transmissivematerial. Optionally, the device includes the same number of samplevessels as collection channels. Optionally, the device includes the samenumber of adaptor channels as collection channels. Optionally, the basecontains an optical indicator that provides a visual indication ofwhether the sample has reached the sample vessel in the base.Optionally, the base is a window that allows a user to see the vessel inthe base. Optionally, the support comprises a spring, and spring exertsa force so that the device is at the extended state when the device isat its natural state. Optionally, the second opening of the collectionchannel or the adaptor channel is capped by a sleeve, wherein saidsleeve does not prevent movement of bodily fluid via capillary actionfrom the first opening towards the second opening. Optionally, thesleeve contains a vent. Optionally, each collection channel can hold avolume of no greater than 500 uL. Optionally, each collection channelcan hold a volume of no greater than 200 uL. Optionally, each collectionchannel can hold a volume of no greater than 100 uL. Optionally, eachcollection channel can hold a volume of no greater than 70 uL.Optionally, each collection channel can hold a volume of no greater than500 uL. Optionally, each collection channel can hold a volume of nogreater than 30 uL. Optionally, the internal circumferential perimeterof a cross-section of each collection channel is no greater than 16 mm.Optionally, the internal circumferential perimeter of a cross-section ofeach collection channel is no greater than 8 mm. Optionally, theinternal circumferential perimeter of a cross-section of each collectionchannel is no greater than 4 mm. Optionally, the internalcircumferential perimeter is a circumference. Optionally, the devicecomprises a first and a second collection channel, and the opening ofthe first channel is adjacent to an opening of said second channel, andthe openings are configured to draw blood simultaneously from a singledrop of blood. Optionally, the opening of the first channel and theopening of the second channel have a center-to-center spacing of lessthan or equal to about 5 mm. Optionally, each sample vessel has aninterior volume no greater than twenty times larger than the interiorvolume of the collection channel with which it is engagable. Optionally,each sample vessel has an interior volume no greater than ten timeslarger than the interior volume of the collection channel with which itis engagable. Optionally, each sample vessel has an interior volume nogreater than five times larger than the interior volume of thecollection channel with which it is engagable. Optionally, each samplevessel has an interior volume no greater than two times larger than theinterior volume of the collection channel with which it is engagable.Optionally, establishment of fluidic communication between thecollection channel and the sample vessel results in transfer of at least90% of the bodily fluid sample in the collection channel into the samplevessel.

It should be understood that one or more of the following features maybe adapted for use with any of the embodiments described herein.Optionally, establishment of fluidic communication between thecollection channel and the sample vessel results in transfer of at least95% of the bodily fluid sample in the collection channel into the samplevessel. Optionally, establishment of fluidic communication between ofthe collection channel and the sample vessel results in transfer of atleast 98% of the bodily fluid sample in the collection channel into thesample vessel. Optionally, establishment of fluidic communicationbetween the collection channel and the sample vessel results in transferof the bodily fluid sample into the sample vessel and in no more thanten μL of bodily fluid sample remaining in the collection channel.Optionally, establishment of fluidic communication between thecollection channel and the sample vessel results in transfer of thebodily fluid sample into the sample vessel and in no more than five μLof bodily fluid sample remaining in the collection channel. Optionally,engagement of the collection channel with the sample vessel results intransfer of the bodily fluid sample into the sample vessel and in nomore than 2 μL of bodily fluid sample remaining in the collectionchannel.

In another embodiment described herein, a method is provided comprisingcontacting one end of a sample collection device to a bodily fluidsample to split the sample into at least two portions by drawing thesample into at least two collection channels of the sample collectiondevice by way of a first type of motive force; establishing fluidcommunication between the sample collection channels and the samplevessels after a desired amount of sample fluid has been confirmed to bein at least one of the collection channels, whereupon the vesselsprovide a second motive force different from the first motive force tomove each of the portions of bodily fluid sample into their respectivevessels.

In another embodiment described herein, a method is provided comprisingmetering a minimum amount of sample into at least two channels by usinga sample collection device with at least two of the sample collectionchannels configured to simultaneously draw the fluid sample into each ofthe at least two sample collection channels via a first type of motiveforce; after a desired amount of sample fluid has been confirmed to bein the collection channels, fluid communication is established betweenthe sample collection channels and the sample vessels, whereupon thevessels provide a second motive force different from the first motiveforce use to collect the samples to move bodily fluid sample from thechannels into the vessels.

In another embodiment described herein, a method of collecting a bodilyfluid sample is provided comprising (a) contacting a bodily fluid samplewith a device comprising a collection channel, the collection channelcomprising a first opening and a second opening, and being configured todraw a bodily fluid via capillary action from the first opening towardsthe second opening, such that the bodily fluid sample fills thecollection channel from the first opening through the second opening;(b) establishing a fluid flow path between the collection channel andthe interior of a sample vessel, said sample vessel having an interiorvolume no greater than ten times larger than the interior volume of thecollection channel and having a vacuum prior to establishment of thefluid flow path between the collection channel and the interior of thesample vessel, such that establishment of the fluid flow path betweenthe collection channel and the interior of the sample vessel generates anegative pressure at the second opening of the collection channel, andthe fluidic sample is transferred from the collection channel to theinterior of the sample vessel.

In another embodiment described herein, a method of collecting a bodilyfluid sample is provided comprising (a) contacting a bodily fluid samplewith any collection device as described herein, such that the bodilyfluid sample fills the collection channel from the first opening throughthe second opening of at least one of the collection channel(s) in thedevice; and (b) establishing a fluid flow path between the collectionchannel and the interior of the sample vessel, such that establishing afluid flow path between the collection channel and the interior of thesample vessel generates a negative pressure at the second opening of thecollection channel, and the fluidic sample is transferred from thecollection channel to the interior of the sample vessel.

It should be understood that one or more of the following features maybe adapted for use with any of the embodiments described herein.Optionally, the collection channel and the interior of the sample vesselare not brought into fluid communication until the bodily fluid reachesthe second opening of the collection channel. Optionally, the devicecomprises two collection channels, and the collection channels and theinterior of the sample vessels are not brought into fluidiccommunication until the bodily fluid reaches the second opening of bothcollection channels. Optionally, the second opening of the collectionchannel in the device is configured to penetrate the cap of the samplevessel, and wherein a fluidic flow path between the second opening ofthe collection channel and the sample vessel is established by providingrelative movement between the second opening of the collection channeland the sample vessel, such that the second opening of the collectionchannel penetrates the cap of the sample vessel. Optionally, the devicecomprises an adaptor channel for each collection channel in the device,the adaptor channel having a first opening and a second opening, thefirst opening being configured to contact the second opening of thecollection channel, and the second opening being configured to penetratethe cap of the sample vessel, and wherein a fluidic flow path betweenthe collection channel and the sample vessel is established by providingrelative movement between two or more of: (a) the second opening of thecollection channel, (b) the adaptor channel, and (c) the sample vessel,such that the second opening of the adaptor channel penetrates the capof the sample vessel.

In another embodiment described herein, a method for collecting a bodilyfluid sample from a subject is provided comprising: (a) bringing adevice comprising a first channel and a second channel into fluidiccommunication with a bodily fluid from the subject, each channel havingan input opening configured for fluidic communication with said bodilyfluid, each channel having an output opening downstream of the inputopening of each channel, and each channel being configured to draw abodily fluid via capillary action from the input opening towards theoutput opening; (b) bringing, through the output opening of each of thefirst channel and the second channel, said first channel and said secondchannel into fluidic communication with a first vessel and a secondvessel, respectively; and (c) directing said bodily fluid within each ofsaid first channel and second channel to each of said first vessel andsecond vessel with the aid of: (i) negative pressure relative to ambientpressure in said first vessel or said second vessel, wherein saidnegative pressure is sufficient to effect flow of said bodily fluidthrough said first channel or said second channel into its correspondingvessel, or (ii) positive pressure relative to ambient pressure upstreamof said first channel or said second channel, wherein said positivepressure is sufficient to effect flow of said whole blood sample throughsaid first channel or said second channel into its corresponding vessel.

In another embodiment described herein, a method of manufacturing asample collection device is provided comprising forming one portion of asample collection device having at least two channels configured tosimultaneously draw the fluid sample into each of the at least twosample collection channels via a first type of motive force; formingsample vessels, whereupon the vessels are configured to be coupled tothe sample collection device to the provide a second motive forcedifferent from the first motive force use to collect the samples to movebodily fluid sample from the channels into the vessels.

In another embodiment described herein, computer executable instructionsare provided for performing a method comprising: forming one portion ofa sample collection device having at least two channels configured tosimultaneously draw the fluid sample into each of the at least twosample collection channels via a first type of motive force.

In another embodiment described herein, computer executable instructionsfor performing a method comprising: forming sample vessels, whereuponthe vessels are configured to be coupled to the sample collection deviceto provide a second motive force different from the first motive forceuse to collect the samples to move bodily fluid sample from the channelsinto the vessels.

In yet another embodiment described herein, a device for collecting abodily fluid sample from a subject, the device comprising: means fordrawing the bodily fluid sample into the device from a single end of thedevice in contact with the subject, thereby separating the fluid sampleinto two separate samples; means for transferring the fluid sample intoa plurality of sample vessels, wherein the vessels provide a motiveforce to move a majority of the two separate samples from the pathwaysinto the vessels.

While the above is a complete description of the preferred embodiment asdescribed herein, it is possible to use various alternatives,modifications and equivalents. Therefore, the scope of the presentinvention should be determined not with reference to the abovedescription but should, instead, be determined with reference to theappended claims, along with their full scope of equivalents. Anyfeature, whether preferred or not, may be combined with any otherfeature, whether preferred or not. The appended claims are not to beinterpreted as including means-plus-function limitations, unless such alimitation is explicitly recited in a given claim using the phrase“means for.” It should be understood that as used in the descriptionherein and throughout the claims that follow, the meaning of “a,” “an,”and “the” includes plural reference unless the context clearly dictatesotherwise. Also, as used in the description herein and throughout theclaims that follow, the meaning of “in” includes “in” and “on” unlessthe context clearly dictates otherwise. Finally, as used in thedescription herein and throughout the claims that follow, the meaningsof “and” and “or” include both the conjunctive and disjunctive and maybe used interchangeably unless the context expressly dictates otherwise.Thus, in contexts where the terms “and” or “or” are used, usage of suchconjunctions do not exclude an “and/or” meaning unless the contextexpressly dictates otherwise. The following US patent applications areincorporated herein by reference for all purposes: 61/733,886 filed Dec.5, 2012, 61/875,030 filed Sep. 7, 2013, 61/875,107 filed Sep. 8, 2013,and 62/239,636 filed on Oct. 9, 2015. This document contains materialsubject to copyright protection. The copyright owner (Applicant herein)has no objection to facsimile reproduction of the patent documents anddisclosures, as they appear in the US Patent and Trademark Office patentfile or records, but otherwise reserves all copyright rights whatsoever.The following notice shall apply: Copyright 2013-2015 Theranos, Inc.

What is claimed is:
 1. A method comprising: receiving, in a channel, abodily fluid sample provided by a subject; mixing the bodily fluidsample with an anticoagulant to generate a mixed bodily fluid sample;and collecting, in a vessel in fluid communication with the channel, themixed bodily fluid sample, wherein the anticoagulant comprises EDTA, andwherein the mixed bodily fluid sample comprises a bulk concentration ofEDTA no less than about 2.5 milligrams per milliliter and no greaterthan about 10 milligrams per milliliter, wherein a concentration of theanticoagulant coating varies along a length of the channel according toa gradient.
 2. The method of claim 1, wherein mixing the bodily fluidsample with the anticoagulant comprises mixing the bodily fluid samplewith the anticoagulant without generating a local concentration of EDTAgreater than about 1121110 milligrams per milliliter.
 3. The method ofclaim 1, wherein the mixed bodily fluid sample reaches the bulkconcentration of EDTA at a time less than 90 seconds after the bodilyfluid sample was initially received in the channel.
 4. A methodcomprising: receiving, in a channel, a bodily fluid sample provided by asubject; mixing the bodily fluid sample with an anticoagulant togenerate a mixed bodily fluid sample; and collecting, in a vessel influid communication with the channel, the mixed bodily fluid sample,wherein the anticoagulant comprises heparin, and wherein the mixedbodily fluid sample comprises a bulk concentration of heparin no lessthan about 20 units per milliliter and no greater than about 150 unitsper milliliter, wherein a thickness of the anticoagulant coating variesalong a length of the channel according to a gradient.
 5. The method ofclaim 4, wherein the mixed bodily fluid sample reaches the bulkconcentration of heparin at a time less than 90 seconds after the bodilyfluid sample was initially received in the channel.
 6. The method ofclaim 4, wherein mixing the bodily fluid sample with the anticoagulantcomprises mixing the bodily fluid sample with the anticoagulant with ashear rate no greater than about 1,000 reciprocal seconds.
 7. A methodcomprising: receiving, in a channel, a bodily fluid sample provided by asubject; mixing the bodily fluid sample with an anticoagulant togenerate a mixed bodily fluid sample; and collecting, in a vessel influid communication with the channel, the mixed bodily fluid sample,wherein the anticoagulant comprises EDTA, and wherein the mixed bodilyfluid sample comprises a bulk concentration of EDTA no less than about2.5 milligrams per milliliter and no greater than about 10 milligramsper milliliter, wherein a concentration of the anticoagulant coatingvaries along a length of the channel according to a gradient; whereinmixing the bodily fluid sample with the anticoagulant comprises mixingthe bodily fluid sample with the anticoagulant with a shear rate nogreater than about 1,000 reciprocal seconds.